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Diet Composition - Alkaline Diet
Category: Food / Nutrients
Practice Questions
Q1: Is the acid produced from the modern Western diet detrimental to calcium balance?
Subcategory: Intervention
Updated: 2016-11-04
Key Practice Point #1
Evidence Synthesis
Evidence from systematic reviews and a meta-analysis does not support the hypothesis that a higher
dietary acid load is detrimental to calcium balance or the retention of whole body calcium, or that an
alkaline diet is supportive of calcium balance. {grade_a}
There is a lack of evidence of a detrimental effect of dietary acid load from high protein diets on bone
health {grade_a}. However, evidence from one systematic review has shown indications of a positive
association between protein intake and bone health {grade_b}.
Grade of Evidence: A & B
Practice Guidance
According to the acid-ash hypothesis, high protein diets lead to increased dietary acid load, which has
been proposed to decrease osteoblastic activity and increase osteoclastic activity, resulting in net bone
resorption with mobilization of calcium. However, there is a lack of evidence to confirm the validity of these
theories as there are no established associations between high protein diets and the disruption of calcium
balance or of its detrimental effect on bone health, expect in the context of inadequate calcium supply.
Adequate intake of vitamin D is recommended as it aids appropriate intestinal absorption of calcium, when
required.
Evidence
a.
A meta-analysis limited to randomized cross-over studies of superior methodological quality in
healthy adults found that in spite of a linear relationship between net acid excretion and urine
calcium, there was no relationship between change of net acid excretion and change of calcium
balance (P=0.38; power=94%) or with N-terminal telopeptides values, a marker of a bone
metabolism (1). The results of this meta-analysis did not support the concept that the increased
urine calcium associated with altered net acid excretion represents the loss of whole body
calcium. The only studies that met the inclusion criteria for this meta-analysis were randomized
control trials (RCTs) of the type (animal versus vegetable) or amount (RDA level intake versus
a higher intake) of protein to alter the diet acid load. No studies that met the inclusion criteria
increased vegetable and fruit intakes. This study did not provide information regarding other
methods to alter net acid excretion on calcium balance.
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b.
A systematic review was conducted to evaluate causal relationships between dietary acid load
and osteoporosis using Hill’s criteria (2). Fifty-five of 238 studies met the inclusion criteria: 22
randomized interventions, two meta-analyses, and 11 prospective observational studies of bone
health outcomes including urine calcium excretion, calcium balance or retention, changes of
bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes
were manipulated or observed through foods or supplements and 19 in vitro cell studies, which
examined the hypothesized mechanism. Urine calcium excretion rates were consistent with
osteoporosis development; however, calcium balance studies did not demonstrate loss of whole
body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash
hypothesis were uncovered; no intervention studies provided direct evidence of osteoporosis
progression (fragility fractures, or bone strength as measured using biopsy). The supporting
prospective cohort studies were not controlled regarding important osteoporosis risk factors
including: weight loss during follow up, family history of osteoporosis, baseline bone mineral
density, and estrogen status. No study revealed a biologic mechanism functioning at
physiological pH. Randomized studies did not provide evidence for an adverse role of phosphate,
sodium, milk and grain foods in osteoporosis.
c.
A systematic review summarized the effects of high protein (HP) diets on bone health and renal
function (3). In this review, no clinical data was found to support detrimental effects of an HP diet
on bone health. Controlled feeding studies comparing high and low protein diets showed that
urinary pH was reduced by 0.3-0.8 units when protein intake was increased by 40 to 60 g/day.
The authors suggested that acid excretion induced by higher protein intakes may be due to the
nature of the ingested proteins because renal net acid-excretion was positively associated with
non-dairy and total animal protein intake but not with plant protein intake. HP diets did induce an
increase in net acid and urinary calcium excretion. However, increased renal acid load was not
found to be associated with modifications of the systemic acid load because plasma pH and
bicarbonate concentrations remained within normal ranges when protein intake was increased to
164 g/day or 2 g/kg/day. This preservation of the systemic acid-base equilibrium suggests that
protein-induced acid load is handled by kidneys through excretion of excess acid and by
activation of the buffer systems. Studies included in this review regarding protein intake and bone
health suggest that HP diets promote bone growth and reduce bone loss, whereas low protein
diets were associated with a higher risk of hip fractures. There was some evidence that the
beneficial effect of protein intake on bone mass is better when both calcium and vitamin D levels
are adequate. All of these findings suggest that high dietary protein intake promotes bone growth
and retards bone loss while a low protein diet is associated with higher risk of hip fractures.
Comments
The 2010 meta-analysis (1) included only studies that followed the recommended practices for calcium
balance studies for the study of calcium metabolism (4) and randomized the subjects to the interventions
to limit the potential for bias because of poor study design. (See Additional Content: Diet Composition Alkaline Diet Background for more information on calcium balance studies). By avoiding major potential
sources of bias due to including non-randomized or poorly controlled studies, this meta-analysis provides
a more accurate estimate of the effect of changes of net acid excretion on calcium balance. The sample
size was sufficiently large enough to be able to detect a relationship between net acid excretion and
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PAGE 2
calcium balance, if a relationship existed.
One frequently quoted balance study (5), not included in the meta-analysis, found superior calcium
balance among postmenopausal women given potassium bicarbonate supplements but it had some
limitations so its findings and use as evidence are questionable. The investigators gave the potassium
bicarbonate supplements under the premise that bicarbonate would neutralize the acid of the modern diet.
However, this study had three limitations in its design, which together likely biased the study findings.
First, the calcium supplement provided to the women had a low bioavailability (7% absorption) (6).
Second, the study did not randomize the order of the intervention, i.e. all subjects received the supplement
and the placebo in the same order. The degree of individual’s adaption to the low bioavailable calcium
supplement between the two interventions could explain the difference seen between the study arms.
Third, the authors make conclusions about the effect of altering protein intakes when potassium
bicarbonate was the intervention, which is scientifically inappropriate. With these limitations, this study
should not be considered confirmation of the acid-ash hypothesis.
Rationale
According to the acid-ash hypothesis, high protein diets lead to increased dietary acid load because
metabolism of dietary proteins contributes to endogenous acid production via oxidation of sulfur amino
acids and phosphoproteins (3). In response, phosphates and carbonates (calcium reservoirs in the body)
are thought by some to be released into the systemic circulation to maintain pH homeostasis in the blood.
Urinary calcium and acid excretion are proposed to be associated with creating a favorable environment for
demineralization of the bone. Dietary acid load has also been proposed to decrease osteoblastic activity
and increase osteoclastic activity, resulting in net bone resorption with mobilization of calcium. However,
these theories have little to no experimental evidence to confirm their validity. There are no established
associations between high protein diets and disruption of the calcium balance as there are regulatory
factors which compensate for urinary calcium loss, and increased urinary calcium may be due to greater
calcium absorption. Furthermore, no experimental or clinical data supports this theory of a detrimental
effect of HP diet on bone health, except in the context of inadequate calcium supply. On the contrary,
there are indications of a positive relationship between protein intake and bone health (1,3).
Adequate intake of vitamin D is recommended as it aids appropriate intestinal absorption of calcium,
magnesium and phosphate when required (7).
References
1.
Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DA. Meta-analysis of the effect of the acidash hypothesis of osteoporosis on calcium balance. J Bone Miner Res. 2009;24(11):1835-40.
Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/19419322
2.
Fenton TR, Tough SC, Lyon AW, Eliasziw M, Hanley DA. Causal assessment of dietary acid
load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria
for causality. Nutr J. 2011 Apr 30;10:41. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/21529374
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3.
Calvez J, Poupin N, Chesneau C, Lassale C, Tomé D. Protein intake, calcium balance and
health consequences. Eur J Clin Nutr. 2012 Mar;66(3):281-95. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/22127335
4.
Institute of Medicine. Dietary Reference Intakes for calcium, phosphorous, magnesium, vitamin D
and fluoride. Washington, D.C.: The National Academies Press; 1997. Available
from: http://www.nap.edu/openbook.php?isbn=0309063507
5.
Sebastian A, Harris ST, Ottaway JH, Tood KM, Morris RC, Jr. Improved mineral balance and
skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Eng J
Med. 1994;330(25):1776-81. Citation available
from: https://www.ncbi.nlm.nih.gov/pubmed/8015587
6.
Wood RJ. Potassium bicarbonate supplementation and calcium metabolism in postmenopausal
women: are we barking up the wrong tree? Nutr Rev. 1994;52(8 Pt 1):278-80. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/7970292
7.
Trautvetter U, Neef N, Leiterer M, Kiehntopf M, Kratzsch J, Jahreis G. Effect of calcium
phosphate and vitamin D₃ supplementation on bone remodelling and metabolism of calcium,
phosphorus, magnesium and iron. Nutr J. 2014 Jan 17;13:6. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/24438153/
Q2: Does an alkaline diet have a role in the risk, prevention, or treatment of chronic diseases
such as obesity, cardiovascular disease, hypertension and diabetes?
Subcategory: Intervention
Updated: 2016-11-04
Key Practice Point #1
No evidence was found from randomized controlled trials or systematic reviews to support the assertions
that an alkaline diet or changing the dietary acid load may prevent or cure chronic diseases such as
obesity and cardiovascular disease. {grade_d}
Literature on dietary acid load (based on the ratio of acid- and base- producing foods and not serum or
urinary pH) estimations show inconsistent results on the association between a higher acid production
from the modern Western diet and an increased risk of hypertension or cardiovascular disease risk
factors. (See Comments) {grade_c}
There is no experimental evidence to validate theories about proposed mechanisms relating influence of
dietary acid load on obesity, hypertension, or cardiovascular disease. {grade_d}
Grade of Evidence: C & D
Evidence
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a.
An observational cohort study examined the relationship between the diet-dependent acid load,
as estimated using a food frequency questionnaire, and the risk of developing hypertension
among 87,293 women in the Nurses’ Health Study over 14 years of follow up (1). Diet-dependent
net acid load was estimated using the net endogenous acid production formula (NEAP). Women
in the top decile of estimated diet-dependent net acid load had an increased risk of hypertension
(relative risk: 1.14; 95%CI, 1.05 to 1.24; P=0.01) compared with women in the bottom decile.
However, while this study controlled for a number of potential confounding variables (age, BMI,
physical activity, oral contraceptive use, smoking, energy intake, calcium intake, alcohol, and
intake), certain variables (weight changes over the follow-up time, menopausal status, hormone
replacement therapy use, family history of hypertension) were not controlled (1). It is possible
that the association noted was due to a mechanism other than the diet-dependent acid load
since the subjects may have had less hypertension due to their higher fruit and vegetable intakes
(for reasons other than the alkalinizing effect on their urine), kept their weight stable, lost weight,
and/or took hormone replacement therapy.
b.
A prospective cohort study examined whether dietary acid load was associated with risk of
hypertension in older Dutch adults from the Rotterdam Study (2). The study included 2241
participants aged ≥55 years who did not have hypertension at baseline and had complete dietary
data on a 170-item food-frequency questionnaire and data on blood pressure. Dietary acid load
was characterized by i) the potential renal acid load (PRAL) measured using an algorithm
including protein, phosphorus, potassium, calcium and magnesium; and ii) the estimated net
endogenous acid production (NEAP) based on protein and potassium. Blood pressure was
measured to determine average at baseline, after two years of follow up, and after six years of
follow up. During 8,707 person-years of follow up, 1113 incidents of hypertension were identified.
Dietary acid load measured with PRAL ranged from alkaline (-14.6 mEq/d) to acidic (19.9
mEq/d), whereas NEAP ranged from 30.4 to 43.7 mEq/d, showing that the diet in the study
population was classified as relatively ‘alkaline’. These findings for dietary acid load were not
associated with the six-year risk of incident hypertension risk and hence there was no evidence
found of an increased risk of hypertension in older adults with relatively low dietary acid load.
Given that these healthy adults were already consuming a relatively ‘alkinalizing’ diet, a further
reduction in PRAL may not have been sufficient to significantly change hypertension risk (2).
This study’s limitations include low number of BP measurements leading to the potential of
measurement errors in BP assessment. Furthermore, information on diet was only collected at
baseline which creates a potential for bias as participants with elevated BP or other medical
issues may have adopted healthier diets in the period over which this study was conducted.
While protein intake increased with higher dietary acid load, potassium intake did not differ
between PRAL tertiles. Additionally, magnesium intake, which should contribute to a lower
dietary acidity, increased with increasing PRAL tertiles. It is suggested that more prospective
cohort studies and RCTs are required to assess the role of dietary acid load in the development
of hypertension in other populations.
c.
A cross-sectional study examined the association between dietary acid load and hypertension
using estimations from nutrient intake in Japanese adults (3). Data was derived from health
surveys of 2,028 individuals (age range: 18-70 years) from two workplaces in Japan. Dietary
assessment was conducted using a validated diet history questionnaire and measures used to
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characterize dietary acid load were PRAL and estimated NEAP. Shift workers were excluded
because shift work is a known risk for hypertension. Prevalence of hypertension was found to be
25% and median PRAL and NEAP were 9.0 (3.6-13.6) mEq/d and 52.1 (45.3-60.0) mEq/d,
respectively. A strong correlation between PRAL and NEAP was found (r=0.96; P<0.001) and
both were positively associated with intake of total fat, animal fat, total protein, animal protein
and sodium intake, and inversely associated with plant fat, plant protein, fibre, potassium,
calcium and magnesium intake. For food groups, PRAL and NEAP were positively associated
with intake of meat, fish, egg and rice but inversely associated with intake of dairy, fruit and
vegetables. Higher levels of dietary acid load assessed by NEAP were found to have a positive
association with increased prevalence odds of hypertension. This finding was only statistically
significant among normal-weight (BMI<23 kg/m2) workers as participants in the highest tertile of
NEAP showed 64% higher odds of hypertension than those in the lowest tertile (P for
trend=0.035; P for interaction=0.65). Generally, workers in the highest tertile of NEAP showed a
41% increased odds of hypertension than those in the lowest tertile (P for trend=0.041; P for
interaction=0.36). Overall, a high dietary acid load was found to be associated with hypertension
in normal weight and non-shift workers. Although possible confounding factors (smoking,
physical activity, sex, alcohol intake, shift-work, parental history of hypertension, sodium intake)
were controlled, PRAL and NEAP were estimated from one-time self-reported dietary intake,
which increases the possibility of bias (3). It is possible that the associations noted were due to
any of the associated intakes of total fat, animal fat, total protein, animal protein and sodium
intake, and/or plant fat, plant protein, fibre, potassium, calcium and magnesium intake rather
than due to the acid load, as this study did not control for these associated factors. This study
also did not control for other hypertension risk factors such as stress, tobacco exposure, and
sleep apnea.
d.
A cross-sectional study examined the association between dietary acid load and
cardiometabolic risk in free-living young Japanese women (n=1136, age range: 18-22 years) (4).
Dietary acid load was measured using PRAL and the ratio of dietary protein to potassium (Pro:K)
with estimates of each nutrient being derived from a validated comprehensive self-administered
diet history questionnaire. Data on anthropometric measurements and blood pressure was
collected. Mean PRAL was found to be 10.4 mEq/d and mean Pro:K was 1.23 g/mEq, with a
strong correlation between these two variables (Pearson correlation coefficient=0.84) indicating
that measures captured similar elements of dietary acid-base load. High PRAL and Pro:K (high
acidic dietary acid-base loads) were found to be associated with higher systolic and diastolic
blood pressure after adjusting for some possible confounders (size of residential area, survey
year, smoking status, physical activity, BMI, waist circumference). Mean difference between
lowest and highest quintiles of dietary acid-load measures was 2.1 mmHg (P for trend=0.028)
and 1.6 mmHg (P for trend=0.035) for PRAL and 2.5 mmHg (P for trend=0.012) and 2.3 mmHg
(P for trend=0.009) for Pro:K, respectively. Independent positive associations were also found
between PRAL and total and LDL-cholesterol, as well as between Pro:K and BMI and waist
circumference (4). This study did not control for a number of cardiometabolic risk factors such as
stress, estimate glomerular filtration rate, sleep apnea, tobacco exposure, alcohol intake, family
history of hypertension and the use of oral contraceptives or hormone replacement therapy.
e.
A cross-sectional study investigated the association between dietary acid load with
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cardiometabolic risk factors in adults (n=5620, age range: 19-70 years) residing in Iran (5).
Dietary data was collected using a validated food frequency questionnaire and PRAL and Pro:K
ratio were identified. Anthropometric measures, blood pressure, serum triglycerides, high density
lipoprotein cholesterol (HDL-C), serum creatinine and fasting blood glucose were recorded and
cardiometabolic risk factors were defined according to the diagnostic criteria by NCEP ATP III.
Participant characteristics and prevalence of metabolic syndrome were compared across
quartiles of dietary PRAL. Results showed that overall mean PRAL was -22.0±29.1 and mean
PRAL in men was -15.6 and -26.8 in women. PRAL and Pro:K were found to be associated with
cardiometabolic risk factors. PRAL was associated with weight (β=0.1; P< 0.01), waist
circumference (β=0.7; P<0.01), serum triglyceride concentration (β=0.03; P<0.05), HDL-C (β=0.08; P<0.01), systolic BP (β=0.05; P< 0.01), diastolic BP (β=0.05; P<0.01) and serum
creatinine (β=0.13; P<0.01). Pro:K ratio was associated with waist circumference (β=0.03;
P<0.01), HDL-C (β=-0.06; P<0.01), serum triglycerides (β=0.03; P<0.05) and systolic blood
pressure (β=0.03; P<0.01). Both measures of dietary acid-base load showed possible
associations with cardiometabolic risk factors. Based on these findings, it was suggested that
higher PRAL and Pro:K ratio or more acidic dietary acid-base load due to high consumption of
meat, grains, egg, fish and dairy products may be associated with increased blood pressure as
well as some other cardiometabolic risk factors in this population. It must be noted; however,
that PRAL and Pro:K were estimated from self-reported dietary intake which could increase the
possibility of bias (5). This study also did not control for the cardiometabolic risk factors such as
family history of hypertension, physical activity, tobacco exposure, alcohol intake, stress factors,
and estimated glomerular filtration rate.
f.
A cross-sectional and longitudinal study aimed to determine if dietary acid load is associated
with incidence of hypertension or blood pressure in older men (6). Kidney function of individuals
was taken into account in this study. In total, 673 men aged 70 to 71 from the Uppsala
Longitudinal Study of Adult Men were included and of these, 378 men were re-examined in the
longitudinal analysis after a seven-year period. Exclusion criteria included unavailability of data,
extreme values of reported energy intake, unavailability of serum cystatin C, use of
antihypertensive medication, and missing BP measures. Dietary acid load was estimated at
baseline by PRAL and NEAP based on seven-day food records taken at baseline. Ambulatory
blood pressure monitoring (ABPM) was conducted at both visits and cystatin C-estimated kidney
function was used to identify underlying chronic kidney disease. Results showed that PRAL and
NEAP were 3.3 mEq/d (IQR: -1.9-9.3; range: -31-34) and 40.7 mEq/d (IQR: 35.6-45.5; range:
17.7 to 65.9), respectively. PRAL was not associated with ABPM measurements (all P>0.05,
except for 24h diastolic blood pressure) and did not predict ABPM changes (P>0.05). Kidney
function did not modify these findings and similar findings were seen with NEAP measurements
showing that there was no association between dietary acid load and blood pressure (6). It
should be noted that dietary data was collected at baseline with the assumption that diet was
constant over the long term. This assumption could be false in terms of the elderly population as
growing health problems can lead to changes in nutritional intake over the years. This study did
not control for the hypertension risk factors such as stress, family history of hypertension,
tobacco exposure and sleep apnea.
g.
A prospective cohort study aimed to investigate the association of dietary acid load with the risk
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PAGE 7
of all-cause and cardiovascular disease mortality (7). Data was taken from two prospective
cohorts, the Swedish Mammography Cohort and the Cohort of Swedish Men which included
36,740 women and 44,957 men aged 45-84 years at the start of the 15-year follow-up period
(1998-2012). Dietary acid load was calculated using PRAL based on a 96-item food frequency
questionnaire that had been validated in a randomly selected population sample from the study
area. Death was assessed using the Cause of Death Register at the National Board of Health
and Welfare. During follow up (mean 13.5±3.3 years) there were 8,576 deaths in women and
13,332 deaths in men, with 3,203 and 5,427 due to cardiovascular disease in women and men,
respectively. Median PRAL values were 0.65 mEq/d for women and 12.3 mEq/d for men, showing
the study population had a relatively ‘alkaline diet’. High PRAL and low PRAL were associated
with higher mortality rates (U-shaped relation) for all-cause and cardiovascular mortality in both
sexes. The associations were, however, small in magnitude and the statistical significance was
weak. Compared with a neutral PRAL (0 mEq/d) HR (95%CI) for the 10th (-15.2 mEq/d) and 90th
(15.6 mEq/d) PRAL percentiles were 1.05 (1.01,1.10) and 1.03 (0.98,1.08), respectively in
women. For men the HRs for the 10th (-5.6 mEq/d) and 90th (29.8 mEq/d) PRAL percentiles
were 1.01 (1.00,1.02) and 1.04 (1.00,1.08). For CVD mortality, HR (95%CI) were 1.06 (0.99 to
1.14) and 1.06 (0.99 to 1.13) for the 10th and 90th PRAL percentiles in women. The corresponding
HR for men were 1.01 (0.99 to 1.03) and 1.06 (1.00 to 1.13). Sensitivity analyses excluding
participants with previous diagnosis of cardiovascular disease, diabetes and/or hypertension
showed similar results. The limitations of this study include the lack of biomarkers in plasma or
urine to validate PRAL estimates and the ‘alkaline’ nature of the Swedish diet, which may limit
the generalizability of these results.
h.
A population-based, retrospectively registered, cross-sectional study of 11,601 participants
(4,813 males and 6,788 females; aged 40-79 years) from the Korea National Health and Nutrition
Examination Survey 2008-2011, analyzed the association between diet-induced acid load and
cardiovascular disease (8). Cardiovascular risk was assessed using the atherosclerotic
cardiovascular disease risk (ASCVD) equations from the 2013 American College of Cardiology
guidelines, including the 10-year ASCVD risk score and the Framingham 10-year CVD risk
score, in participants without CVD. Acid-base status was assessed using PRAL and Dietary
Acid Load (DAL [mEq/d] = PRAL + (body surface area [m2] × 41 [mEq/day]/1.73 m2)) derived
from dietary intake information collected by a one-day, in-person, 24-hour recall by trained
interviewers. Both scores were categorized into sex-specific tertiles. Results showed that
individuals in the highest PRAL tertile had a significant increase in the 10-year ASCVD risk (9.6
versus 8.5%, P< 0.01) and belonged to the high risk group (10-year risk >10%) compared to
those in the lowest PRAL tertile (OR=1.23, 95% CI 1.22 to 1.35). Higher PRAL score had a
stronger association with high CVD risk in the middle-aged group (OR=1.20, 95%CI 1.01 to
1.43). When the study population was stratified according to obesity and exercise levels, higher
PRAL scores increased the proportion of ADCVD risk regardless of BMI (OR range: 1.19 to 1.37,
P< 0.05 for all groups) and increased the ASCVD group distribution independent of exercise
status (OR range: 1.23 to 1.27, P<0.05 for all groups). Additionally, the association of elevated
PRAL scores and ASCVD risk was found to be independent of insulin resistance. The authors
concluded that diet-induced acid-load as measured by PRAL and DAL was associated with
increased risk of CVD independent of obesity, insulin resistance, and physical activity (8).
However, it should be noted that dietary intake was based on self-reported data and although this
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PAGE 8
study controlled for certain confounding factors (age, sex, exercise, family history of cardio- and
cerebrovascular disease, diabetes, hypertension, LDL cholesterol, estimated glomerular filtration
rate, urine pH), it did not control for CVD risk factors of menopausal status, tobacco exposure,
use of oral contraceptives or hormone replacement therapy.
Comments
The use of NEAP and PRAL estimations to draw conclusions about systemic acid-base consequences on
the human body remains questionable because there are not only objections about the variables used in
the equations and limited control for confounding, but also that endocrine and metabolic systems maintain
blood pH within a narrow range and diet alone does not induce metabolic acidosis. The human body has
buffer systems, which compensate for diet and endogenous acid generation (9). The use of these formulas
and interpretation of scientific evidence based on these estimations requires caution as inferences made
from these findings may be faulty since pH changes in the urine are not reflective of changes in systemic
pH. Although these methods are considered to be an indirect measurement of urine pH, there is no
convincing scientific evidence to prove that urinary acid excretion impacts the risk of medical conditions.
Rationale
It is hypothesized that high dietary acid load may lead to elevated blood pressure and hypertension
incidence (2). Proposed mechanisms state that a high dietary acid load is associated with
a compensatory increase in renal acid excretion and ammoniagenesis for the maintenance of acid-base
homeostasis. Although these mechanisms are beneficial for maintaining homeostasis in the short term, it
is hypothesized that they may lead to a decline in renal function and raise blood pressure over the long
term (2). However, the argument that the renal system can be overwhelmed by dietary acid load overtime,
is not substantiated by evidence as there have been no studies showing a link between protein-induced
renal hypertrophy or hyper-filtration and the initiation of renal disease in healthy individuals (10). Other
factors proposed linking high dietary acid load and hypertension include increased cortisol production,
increased calcium excretion, reduced citrate excretion, and the association of dietary intake of protein,
potassium and other minerals with increased blood pressure (2). However, these associations have no
experimental evidence to confirm their validity.
References
1.
Zhang L, Curan GC, Forman JP. Diet-dependant net acid load and risk of incident hypertension
in United States women. Hypertension. 2009;54(4):751-5. Abstract available from:
https://www.ncbi.nlm.nih.gov/pubmed/19667248
2.
Engberink MF, Bakker SJ, Brink EJ, van Baak MA, van Rooij FJ, Hofman A, Witteman JC,
Geleijnse JM. Dietary acid load and risk of hypertension: the Rotterdam Study. Am J Clin Nutr.
2012 Jun;95(6):1438-44. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/22552032
3.
Akter S, Eguchi M, Kurotani K, Kochi T, Pham NM, Ito R, Kuwahara K, Tsuruoka H, Mizoue T,
Kabe I, Nanri A. High dietary acid load is associated with increased prevalence of hypertension:
the Furukawa Nutrition and Health Study. Nutrition. 2015 Feb;31(2):298-303. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/25592007
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PAGE 9
4.
Murakami K, Sasaki S, Takahashi Y, Uenishi K; Japan Dietetic Students’ Study for Nutrition and
Biomarkers Group. Association between dietary acid-base load and cardiometabolic risk factors
in young Japanese women. Br J Nutr. 2008 Sep;100(3):642-51. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/18279559
5.
Bahadoran Z, Mirmiran P, Khosravi H, Azizi F. Associations between dietary acid-base load and
cardiometabolic risk factors in adults: the Tehran Lipid and Glucose Study. Endocrinol Metab
(Seoul). 2015 Jun;30(2):201-7. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/25433661
6.
Luis D, Huang X, Riserus U, Sjögren P, Lindholm B, Arnlöv J, Cederholm T, Carrero JJ.
Estimated dietary acid load is not associated with blood pressure or hypertension incidence in
men who are approximately 70 years old. J Nutr. 2015 Feb;145(2):315-21. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/25644353
7.
Xu H, Åkesson A, Orsini N, Håkansson N, Wolk A, Carrero JJ. Modest U-shaped association
between dietary acid load and risk of all-cause and cardiovascular mortality in adults. J Nutr.
2016 Aug;146(8):1580-5. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/27385761
8.
Han E, Kim G, Hong N, Lee YH, Kim DW, Shin HJ, et al. Association between dietary acid load
and the risk of cardiovascular disease: nationwide surveys (KNHANES 2008-2011). Cardiovasc
Diabetol. 2016 Aug 26;15(1):122. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/27565571
9.
Frassetto LA, Lanham-New SA, Macdonald HM, Remer T, Sebastian A, Tucker KL. Et al.
Standardizing terminology for estimating the diet-dependent net acid load to the metabolic
system. J Nutr. 2007;137(6):1491-2. Citation available
from: https://www.ncbi.nlm.nih.gov/pubmed/17513412
10.
Calvez J, Poupin N, Chesneau C, Lassale C, Tomé D. Protein intake, calcium balance and
health consequences. Eur J Clin Nutr. 2012 Mar;66(3):281-95. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/22127335
Key Practice Point #2
No evidence was found from randomized controlled trials or systematic reviews to support the assertions
that an alkaline diet or changing the dietary acid load may prevent or cure type 2 diabetes. {grade_d}.
Literature on dietary acid load (based on the ratio of acid- and base-producing foods and not serum or
urinary pH) estimations show associations between a higher acid production from the modern Western
diet and an increased risk of type 2 diabetes (see Comments). {grade_c}
There is no experimental evidence of to validate the theories about proposed mechanisms on the influence
of dietary acid load on type 2 diabetes. {grade_d}
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Grade of Evidence: C & D
Evidence
a.
A prospective cohort study conducted on the E3N-EPIC cohort of 66,485 women aimed to
evaluate the relationship between dietary acid load and the risk of type 2 diabetes (1). Usual diet
over the previous year was assessed using a validated 208-item diet history questionnaire
according to the French meal pattern and nutrients were estimated using a French food
composition table. Dietary-acid load was assessed using potential renal acid load (PRAL) and
the net endogenous acid production (NEAP) scores. During the 14-year follow up, 1,372 cases of
incident type 2 diabetes were identified, and both PRAL and NEAP scores were associated with
the increased risk in age-adjusted multivariate models. Women with a high acid load
(PRAL>7 mEq/d) were found to be at higher risk than those with high alkaline load ((PRAL<14mEq/d) (HR 1.71; 95%CI, 1.40 to 2.07)). A similar hazards ratio was seen for the NEAP score
between extreme categories (HR 1.74; 95%CI, 1.44 to 2.11). Overall, a high acid load (median
PRAL=-3.0 mEq/d) characterized by a high PRAL or a high NEAP score appeared to be
associated with an increased risk of type 2 diabetes in women. These associations were
stronger in normal-weight women (BMI≤25 kg/m2) (1). However, it should be noted that this study
did not account for changes in dietary habits over time and PRAL and NEAP were only
estimated based on self-reported intake at baseline. This study also did not control for the type
2 diabetes risk factors such as race, body fat distribution, waist circumference, tobacco
exposure, history of polycystic ovarian syndrome and history of gestational diabetes.
b.
A prospective cohort study examined the association between dietary acid load and type 2
diabetes in Japanese adults (2). The study included 27,809 men and 36,851 women, aged 45 to
75 years old from the Japan Public Health Center-based Prospective Study who had completed a
dietary questionnaire and had no history of type 2 diabetes. Dietary data was obtained using a
147-item food frequency questionnaire and the nutrient intake data was used to derive PRAL and
NEAP scores. Over the course of five years, a total of 1,191 cases of newly diagnosed type 2
diabetes were reported. PRAL score was positively associated with type 2 diabetes only in men
under the age of 50 (P trend=0.046) and the multivariable-adjusted ORs (95%CI) for the lowest to
highest quartiles of PRAL were: 1.00, 1.09 (0.87 to 1.36), 1.10 (0.88 to 1.37), and 1.25 (1.01 to
1.55) (P trend=0.047). NEAP score was not associated with risk of T2D (P trend = 0.20). These
findings indicated an association between high dietary acid load estimated by PRAL and an
increased risk of type 2 diabetes (2). However, this study did not control for type 2 diabetes risk
factors such as body fat distribution, waist circumference, hypercholesterolemia, tobacco
exposure, history of polycystic ovarian syndrome and history of gestational diabetes.
c.
An observational study analyzed the association between dietary acid load with insulin
resistance markers, insulin secretion and blood glucose status among Japanese workers (3). In
total, 1,732 workers were recruited (1,563 men and 169 women; age range: 19-69 years). A
health survey and a brief validated diet history questionnaire were used to collect nutrient data
from which PRAL and NEAP scores were derived. Data on fasting insulin, fasting plasma
glucose, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model
assessment of B-cell function (HOMA-B) score and A1C levels was obtained. Results showed a
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PAGE 11
positive association of HOMA-IR score with PRAL (P trend=0.045) and a similar association
between NEAP and HOMA-IR scores (P trend=0.03), specific to individuals with BMI < 23 kg/m2
(P trend=0.03 and 0.01 for PRAL and NEAP, respectively). NEAP was also positively associated
with HOMA-B score (P trend=0.03). These findings indicate that high dietary acid load estimated
by PRAL and NEAP may be associated with insulin resistance in adults classified as healthy by
BMI (3). This study did not control for the type 2 diabetes risk factors such as body fat
distribution, waist circumference, hypercholesterolemia, tobacco exposure, history of polycystic
ovarian syndrome and history of gestational diabetes.
d.
A prospective cohort study of 911 Swedish men aged 70-71 years with an 18-year follow up (4).
The aim was to assess whether dietary acid load increases the risk of type 2 diabetes.
Individuals with diabetes were excluded. PRAL and NEAP were calculated from a seven-day
dietary record. NEAP was calculated two ways (NEAP1 and NEAP2). Adequate dietary reporters
were identified by Goldberg cut-offs. A euglycemic-hyperinsulinemic clamp and oral glucose
tolerance test were used to assess insulin sensitivity and beta cell function respectively.
Although insulin sensitivity tended to decrease with PRAL and NEAP increments, there was no
significant association detected for insulin sensitivity or beta cell function when assessed as part
of three different models adjusted for age, clinical, and dietary factors. Associations for insulin
sensitivity based on the clamp (95%CI) across models 1-3 for PRAL were -0.05 (-0.16 to 0.05), 0.05 (-0.15 to 0.06) and -0.05 (-0.16 to 0.06) and for NEAP1 -0.06 (-0.19 to 0.06), -0.09 (-0.21 to
0.03) and -0.09 (-0.21 to 0.03). Similar nonsignificant results were reported for NEAP2 and for
beta cell function. During follow up, there were 115 new cases of diabetes, but neither PRAL nor
NEAP were associated with diabetes incidence. In a multicategory model the P trend for PRAL
was 0.48, 0.50, 0.41 and 0.71; for NEAP1 it was 0.44, 0.42, 0.28 and 0.43. Similar nonsignificant
results were reported for NEAP2. The strength of this study is the use of the gold standard
euglycemic-hyperinsulinemic clamp to assess insulin sensitivity. However, the cohort was
relatively small and accordingly only 115 incident cases of type 2 diabetes were reported during
follow up, which may limit the power of these findings.
Comments
The use of NEAP and PRAL estimations to draw conclusions about systemic acid-base consequences on
the human body remains questionable because there are not only objections about the variables used in
the equations, but also that endocrine and metabolic systems maintain blood pH. The human body has
buffer systems, which compensate for diet and endogenous acid generation (5). The use of these formulas
and interpretation of scientific evidence based on these estimations requires caution as inferences made
from these findings may be faulty since pH changes in the urine are not reflective of changes in systemic
pH. Although these methods are considered to be an indirect measurement of urine pH, there is no
convincing scientific evidence to prove that urinary acid excretion impacts risk of medical conditions.
Rationale
Mechanisms have been proposed about the influence of dietary acid on the risk of diabetes. It is
hypothesized that an acidogenic diet may over time induce mild metabolic acidosis and lead to insulin
resistance as a result of decreased binding of insulin to its receptors leading to insulin resistance and to
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PAGE 12
decreased insulin secretion (1,7). However, the direct cause and effect relationship between a high acid
load diet, mild metabolic acidosis and risk of insulin resistance and type 2 diabetes has not been
established. Furthermore, metabolic acidosis (blood pH<7.35), is a medical concern, and is equal to
a much larger change in plasma pH than that which occurs from diet changes. The systemic pH change
(0.014 pH units) that occurs due to dietary change (5) is not meaningful, such as 7.40 to 7.414. Normal
systemic pH ranges from 7.35 to 7.45. An alkaline diet does not change blood pH to be outside of the
normal range (6).
References
1.
Fagherazzi G, Vilier A, Bonnet F, Lajous M, Balkau B, Boutron-Rualt MC, Clavel-Chapelon F.
Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study. Diabetologia. 2014
Feb;57(2):313-20. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/24232975
2.
Akter S, Kurotani K, Kashino I, Goto A, Mizoue T, Noda M, Sawada N, Tsugane S; Japan Public
Health Center–based Prospective Study Group. High dietary acid load score Is associated with
increased risk of type 2 diabetes in Japanese men: the Japan Public Health Center-based
Prospective Study. J Nutr. 2016 May;146(5):1076-83. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/27052540
3.
Akter S, Eguchi M, Kuwahara K, Kochi T, Ito R, Kurotani K, et al. High dietary acid load is
associated with insulin resistance: the Furukawa Nutrition and Health Study. Clin Nutr. 2016
Apr;35(2):453-9. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/25863769
4.
Xu H, Jia T, Huang X, Riserus U, Cederholm T, Arnlov J, et al. Dietary acid load, insulin
sensitivity and risk of type 2 diabetes in community-dwelling older men. Diabetologia. 2014;57
(8):1561-8. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/24875749
5.
Frassetto LA, Lanham-New SA, Macdonald HM, Remer T, Sebastian A, Tucker KL. et al.
Standardizing terminology for estimating the diet-dependent net acid load to the metabolic
system. J Nutr. 2007;137(6):1491-2. Citation available
from: https://www.ncbi.nlm.nih.gov/pubmed/17513412
6.
Buclin T, Cosma M, Appenzeller M, Jacquet AF, Decosterd LA, Biollaz J, et al. Diet acids and
alkalis influence calcium retention in bone. Osteoporos Int. 2001;12(6):493-9. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/11446566
7.
Williams RS, Kozan P, Samocha-Bonet D. The role of dietary acid load and mild metabolic
acidosis in insulin resistance in humans. Biochimie. 2016;124:171-7. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/26363101
Q3: Does an alkaline diet prevent or cure cancer?
Subcategory: Intervention
Updated: 2016-11-04
Key Practice Point #1
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PAGE 13
There is no evidence to support that an alkaline diet may prevent or cure cancer. {grade_d}.
Changes in urinary pH are not a major risk factor for bladder cancer. {grade_c}.
Grade of Evidence: C & D
Evidence
a.
A systematic review evaluated evidence on the relationship between dietary acid or alkaline or
alkaline water for the etiology and treatment of cancer (1). Studies selected for the review were of
randomized intervention and observational studies with acid-base dietary intakes and/or alkaline
water for any cancer treatment or outcome. Outcome measures were incidence of cancer and
outcomes of cancer treatment. Out of the 252 abstracts reviewed, one study met the inclusion
criteria and had a low risk of bias assessed on the Newcastle-Ottawa Scale of quality
assessment. No randomized trials (RCTs) were found that examined dietary acid or alkaline
or alkaline water for cancer treatment. The study included was a prospective cohort study of
27,096 male smokers (age range: 50-69 years) designed to examine the relationship between
estimated renal net acid excretion, with bladder cancer risk using observational data from the
Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Net acid excretion was
estimated using a self-administered, validated dietary questionnaire with an estimate of
endogenous acid production based on anthropometry. This method was considered to be an
indirect measurement of urine pH. Results showed that the relative risk (RR) for bladder cancer
was 1.15 (95%CI=0.86 to 1.55) for individuals in the highest (i.e. most acidic) versus the lowest
(i.e. least acidic) net acid excretion quintile (P=0.38) suggesting that urine pH was not a major
risk factor for bladder cancer. Among men who smoked for more than 45 years, there was a
suggestion of increased risk with higher net acid excretion levels (RR=1.72, 95%CI=0.96 to 3.10,
P=0.08). The nonstatistically significant results from this study showed that urine pH is a not a
major risk factor for bladder cancer. This systematic review revealed that there is a lack of
evidence supporting the acid-ash hypothesis that suggests that acid from the diet causes or
contributes to cancer development.
Comments
In response to claims that acidic foods increase the risk of cancer because cancer cells do well in acidic
environment, the American Institute for Cancer Research stated: “These claims stand in stark contrast to
everything we know about the chemistry of the human body. Acid-base balance is tightly regulated by
several mechanisms, among them kidney and respiratory functions. Even slight changes to your body’s
pH are life-threatening events. What you eat can have a profound effect on your cancer risk, but the acidity
or alkalinity of foods is not important” (2).
References
1.
Fenton TR, Huang T. Systematic review of the association between dietary acid load, alkaline
water and cancer. BMJ Open. 2016 Jun 13;6(6):e010438. Abstract available from:
https://www.ncbi.nlm.nih.gov/pubmed/27297008
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PAGE 14
2.
American Institute for Cancer Research. Cancer and acid-base balance: busting the myth.
e.Newsletter. May 2008. Available from: http://www.aicr.org/site/News2?
page=NewsArticle&id=13441
Q4: Does the use of a water alkalinizer to alkalinize and ioinize tap water cure cancer?
Subcategory: Intervention
Updated: 2016-11-04
Key Practice Point #1
A literature review on the use of alkaline water and water alkalinizers for alkalinizing and ionizing tap water
to prevent or cure cancer revealed no human studies regarding alkaline water and cancer. Intake of
alkaline water intake has only been related to inhibited gastric secretion, reduced gallbladder emptying
and toxic reactions in humans, and cardiac necrosis and growth restriction in animal studies.
Grade of Evidence: D
Evidence
a.
A systematic review evaluated the evidence on the relationship between dietary acid or alkaline or
or alkaline water for the etiology and treatment of cancer (1). Studies selected for the review were
of randomized intervention and observational studies with acid-base dietary intakes and/or
alkaline water for any cancer treatment or outcome. Outcome measures were incidence of
cancer and outcomes of cancer treatment. No randomized trials (RCTs) were found that
examined dietary acid or alkaline or alkaline water for cancer treatment. However, the review
found studies of alkaline water treatment and its effects unrelated to cancer. None of these
studies supported the suggestion that alkaline water supports better health. Alkaline water intake
was related to inhibited gastric secretion, reduced gallbladder emptying, and toxic reactions in
humans and cardiac necrosis and growth restriction in rats. Overall, this systematic review
revealed that there is a lack of evidence supporting the acid–ash hypothesis, which suggests
that acid from the diet causes or contributes to cancer development.
Rationale
It is proposed that ‘metabolic alkalosis’ may be useful for enhancing treatment with some chemotherapy
regimens because cell death is associated with increased intracellular alkalinity (2). Hence, extracellular
alkalinzation with the use of sodium bicarbonate, carbicab and furosemide are promoted to improve
therapeutic effectiveness of chemotherapy regimens (2). However, there is no scientific literature to
establish the benefit of an alkaline diet or alkaline water for cancer prevention or enhancing chemotherapy.
These theories have little to no experimental evidence to confirm their validity. Furthermore, metabolic
alkalosis is not achievable through the diet as the systemic pH change (0.014 pH units) (3) that occurs
due to dietary change is not meaningful, such as 7.40 to 7.414. Normal systemic pH ranges from 7.35 to
7.45. An alkaline diet does not change blood pH to be outside of this normal range.
References
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PAGE 15
1.
Fenton TR, Huang T. Systematic review of the association between dietary acid load, alkaline
water and cancer. BMJ Open. 2016 Jun 13;6(6):e010438. Abstract available from:
https://www.ncbi.nlm.nih.gov/pubmed/27297008
2.
Schwalfenberg GK. The alkaline diet: is there evidence that an alkaline pH diet benefits health? J
Environ Public Health. 2012;2012:727630. Abstract available from:
https://www.ncbi.nlm.nih.gov/pubmed/22013455/
3.
Buclin T, Cosma M, Appenzeller M, Jacquet AF, Decosterd LA, Biollaz J, et al. Diet acids and
alkalis influence calcium retention in bone. Osteoporos Int. 2001;12(6):493-9. Abstract available
from: https://www.ncbi.nlm.nih.gov/pubmed/11446566
Q5: Is there a role for the alkaline diet in preventing or curing depression, yeast overgrowth and
cellulite?
Subcategory: Intervention
Updated: 2016-11-04
Key Practice Point #1
There is no evidence to support the assertion that an alkaline diet may prevent or cure depression or yeast
overgrowth or cellulite.
Grade of Evidence: D
Evidence
a.
No published studies were found on the diet-dependent acid load and depression or yeast
overgrowth or cellulite.
Evidence Summary
Diet Composition - Alkaline Diet Evidence Summary
Last Updated: 2016-11-10
[A] The following conclusions are supported by good evidence:
Evidence from systematic reviews and a meta-analysis does not support the hypothesis that a higher
dietary acid load is detrimental to calcium balance or the retention of whole body calcium, or that an
alkaline diet is supportive of calcium balance.
There is a lack of evidence of a detrimental effect of dietary acid load from high protein diets on bone
health.
[B] The following conclusions are supported by fair evidence:
Evidence from one systematic review has shown indications of a positive association between protein
intake and bone health.
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PAGE 16
[C] The following conclusions are supported by limited evidence or expert opinion:
Literature on dietary acid load (based on the ratio of acid- and base- producing foods and not serum or
urinary pH) estimations show inconsistent results on the association between a higher acid production
from the modern Western diet and an increased risk of hypertension or cardiovascular disease risk
factors.
Literature on dietary acid load (based on the ratio of acid- and base-producing foods and not serum or
urinary pH) estimations show associations between a higher acid production from the modern Western
diet and an increased risk of type 2 diabetes.
Changes in urinary pH are not a major risk factor for bladder cancer.
[D] A conclusion is either not possible or extremely limited because evidence is unavailable
and/or of poor quality and/or is contradictory:
No evidence was found from randomized controlled trials or systematic reviews to support the assertions
that an alkaline diet or changing the dietary acid load may prevent or cure chronic diseases such as
obesity and cardiovascular disease.
There is no experimental evidence to validate theories about proposed mechanisms relating influence of
dietary acid load on obesity, hypertension, or cardiovascular disease.
No evidence was found from randomized controlled trials or systematic reviews to support the assertions
that an alkaline diet or changing the dietary acid load may prevent or cure type 2 diabetes.
There is no evidence to support that an alkaline diet may prevent or cure cancer.
A literature review on the use of alkaline water and water alkalinizers for alkalinizing and ionizing tap water
to prevent or cure cancer revealed no human studies regarding alkaline water and cancer. Intake of
alkaline water intake has only been related to inhibited gastric secretion, reduced gallbladder emptying
and toxic reactions in humans, and cardiac necrosis and growth restriction in animal studies.
There is no evidence to support the assertion that an alkaline diet may prevent or cure depression or yeast
overgrowth or cellulite.
Note: See relevant practice questions in this knowledge pathway for references.
Background
Diet Composition - Alkaline Diet Background
Last Updated: 2017-05-03
Importance of Topic to Practice
The alkaline diet (also referred to as the acid-base or the alkaline acid diet) is marketed to the general
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PAGE 17
public as a way to improve health and cure diseases including cancer, obesity, cardiovascular disease,
osteoporosis, diabetes, cellulite and mental illness. This marketing is done via the Internet, alternative
health providers, salespeople, flyers, magazines, direct mail marketing, and books directed to lay
audiences. The concept behind this marketing, the acid-ash hypothesis (also referred to as the acid-base
hypothesis), postulates that the composition of the modern diet results in excess endogenous acid
production, which if not neutralized, causes disease (1). The alkaline diet is not an unhealthy diet per se,
as it is a mostly a vegetarian diet; however, it can be unhealthy if not planned properly or if supplements
are added to promote “alkalinization” (i.e. “alkaline” supplements and water “alkalinizers”). These
supplements are heavily promoted to the public. People inflicted with disease may be susceptible to this
marketing.
The acid-ash hypothesis has been broadly stated as a major modifiable risk factor for age-related bone
loss that results in osteoporosis in well-cited scientific papers (2,3), textbooks (4), and reference works
(5,6).
It is important for dietitians to have an understanding of the alkaline diet, and the lack of evidence
regarding its usefulness in preventing or treating disease.
Topic Overview
Origin
The acid-ash hypothesis gets its name from its origins. Over 100 years ago, early nutrition researchers
analyzed foods by examining all of the minerals in foods as a single substance: the ash (7). When the
organic components of foods are burned off, the only part that remains is the ash. The early analyses of
the ash were simple: dissolve it in water, measure its pH, and define it as acidic or an alkaline. Some
small feeding trials (n=2) of the ash were conducted, with urine examined for pH. In 1907, Sherman
proposed that the excess acidity or alkalinity could be defined by the following equation: Cl 2xPO4 SO4Na-K-2xCa-2xMg in milli-equivalents per day (7). Unfortunately, due to the terminology in the early papers,
there has been on-going confusion in the literature of the hypothesis, in which anions are referred to as
“acids” and cations are referred to as “bases” (8). This equation has remained in the medical literature,
with one minor adaption suggested by Remer and Manz published in 1994 (9).
Acid Production and Excretion Estimation
Acid production and excretion are estimated by the PRAL (potential renal acid load) and NEAP (net
endogenous acid production) in the literature (10). PRAL (mEq) is calculated as [0.49 x protein (g/d)
+ 0.037 x phosphorous (mg/d) – 0.021 x potassium (mg/d) – 0.026 x magnesium (mg/d) – 0.013
x calcium (mg/d)]. A positive PRAL is theorized to be reflective of acid-forming potential and a negative
score is reflective of alkaline-forming potential. The NEAP formula considers dietary intake of protein and
potassium as the determining factor of acid production and is calculated as NEAP (mEq/d) = −10.2 + 54.5
(protein intake [g/d] ÷ potassium intake [mEq/d]) (10). Through these estimates, fruit, vegetables, fruit
juices, potatoes, and beverages, such as red and white wine and mineral soda waters, are classified as
having a negative acid loads; whereas, grain products, meats, dairy, fish, and beverages, such as pale
beers, have high acid loads.
The calculation of PRAL of foods was first developed more than 100 years ago and since then nutrition
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PAGE 18
knowledge about the importance of minerals has expanded (11). Hence, the use of NEAP and PRAL
estimations to draw conclusions about systemic acid-base consequences on the human body remains
questionable because there are not only objections about the variables used in the equations, but
endocrine and metabolic systems maintain blood pH, and these buffer systems interfere with diet and
endogenous acid generation (11).
Premise
Proponents of the alkaline diet have put forth theories about the ways in which an acidic diet could harm
human health. According to the acid-ash hypothesis, diets high in protein lead to increased dietary acid
load because the metabolism of dietary proteins contributes to endogenous acid production via oxidation
of sulfur amino acids and phosphoproteins (12). In response, it is hypothesized that calcium is released
from bones to maintain pH homeostasis in the blood and a more alkaline urinary pH can be detected as
urinary calcium, with increased un-dissociated uric acid and phosphate, thereby creating a favourable
environment for the demineralization of bones (12,13). Dietary acid load has also been proposed to
decrease osteoblastic activity and to increase osteoclastic activity, resulting in net bone resorption with
the mobilization of calcium (12). Also, it is hypothesized that an acidogenic diet may, over time, induce
mild metabolic acidosis, and lead to insulin resistance as a result of decreased binding of insulin to its
receptors and decreased insulin secretion (10,14). Further, the hypotheses include that high dietary acid
load may be linked to hypertension (15). Proposed mechanisms are that a high dietary acid load is
associated with a compensatory increase in renal acid excretion and ammoniagenesis for the
maintenance of acid-base homeostasis, which may eventually lead to a decline in renal function and
cause hypertension over time (16). Other factors proposed in this relationship include increased cortisol
production, increased calcium excretion, reduced citrate excretion, and the association of dietary intake of
protein, potassium and other minerals with increased blood pressure. Lastly, it has also been proposed
that an acidogenic diet promotes cancer as cancer cells do well in acidic environment and that
chemotherapy regimens are more successful in an alkaline environment (13).
Acid-base Balance
The human body has stringent mechanisms to maintain a pH homeostasis of approximately 7.4 to
coordinate function of its systems (i.e. enzymes require a very narrow pH range for optimal function) (17).
This steady blood pH is maintained with compensatory mechanisms that involve renal and respiratory
systems. Therefore, urinary pH can indeed be influenced while balancing the systemic pH and it is
influenced by dietary intake (17). Despite the influence on urinary pH, an alkaline diet does not change
blood pH outside of the normal range (18).
When protein is digested, the metabolism of the amino acids can produce acids depending on the specific
amino acids digested (17). If dietary protein produced net acids, pH is rapidly buffered by bicarbonate ions
in the blood to produce carbon dioxide that is then exhaled through the lungs, and salts that are then
excreted by the kidneys, principally with ammonium (17). During the excretion process of ammonium,
filtered bicarbonate is reabsorbed, and the kidneys replace these bicarbonate ions into the blood, creating
a sustainable cycle to maintain systemic pH (19). The argument that the renal system can be
overwhelmed by dietary acid load overtime, is not substantiated by evidence as there have been no
studies showing a link between protein-induced renal hypertrophy or hyperfiltration and the initiation of
renal disease in healthy individuals (12).
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It is argued that the systemic acid is neutralized by calcium absorbed from the bones, eventually leading
to osteoporosis. However, there are no associations between high protein diets and the disruption of the
calcium balance as scientific literature does not support a detrimental effect of a high protein diet on bone
health (12) or calcium loss (20). On the contrary, protein intake has shown to have a protective effect on
bone health and strength (12). There is also evidence that calcium balance is maintained and improved
with phosphate intake, which contradicts the acid-ash hypothesis (20).
Aforementioned theories associated with metabolic acidosis are based on an invalid premise because
metabolic acidosis, (blood pH < 7.35), is a medical concern, and is equal to a much larger change in
plasma pH than that which occurs from diet changes (21). The systemic pH change (0.014 pH units) that
occurs due to dietary change is not meaningful, such as 7.40 to 7.414 (18). Normal systemic pH ranges
from 7.35 to 7.45. An alkaline diet does not change blood pH to be outside of this normal range.
Relevant Basic Information
Why does the acid-ash hypothesis categorize most foods as undesirable?
Lay writers of the hypothesis consider all phosphate and sulfate ions as “acidic”, undesirable, and needing
to be minimized in the diet, while sodium, potassium, calcium, and magnesium are considered “alkaline”
and desirable (22). Based on the calculations made under the hypothesis, the phosphate, sulfate, and
sulfur-containing amino acid contents of dairy products, most grains, and meat and alternates place these
foods in the “acidic” category.
The limits of the estimation of the diet acid load is described by the researchers who work with the
hypothesis: "we do not address the issue of the accuracy of the estimates given by the exemplified
algorithms, nor do we address the issue of the accuracy of renal net acid excretion as measured by the
excretion of TA + NH4 - HCO3 as a reflection of true NEAP" (11). They state that “investigators wishing to
draw conclusions from NEAP estimation or NAE measurement about systemic acid base consequences
must consider not only objections about the methodologies used in measuring the variables for NEAP or
NAE algorithms, but also that additional endocrine and metabolic effects may interfere with endogenous
acid generation and buffering” (11).
Further, evidence does not support the acid-ash hypothesis concept that phosphate is detrimental to
calcium retention (22). When the acid-ash calculation of whether foods are “acidic” omits phosphate, then
dairy products and grain foods would no longer fall in the undesirable “acidic” category (22). The
consideration of sodium as bone and health supporting is also not proven (23).
Finally, studies of the actual acid load of milk revealed that milk does not produce an “acid” load on
metabolism, rather milk decreases the “acid” load (24). Grains have not been evaluated for their
hypothesized acidogenic and calciuric responses or their effect on bone health, although one attempt has
been made (25). In summary, the acid-ash hypothesis is not compatible with chemistry principles and is
not supported by evidence to categorize foods as undesirable.
What is a calcium balance study?
A calcium balance study provides a more accurate assessment of whole body calcium metabolism than
urine calcium (26). The Institute of Medicine states that to ensure adequate precision of a calcium balance
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PAGE 20
study, the investigators should: i) control the subjects’ calcium intakes for seven or more days prior to
measurement of the outcomes (to allow adaption to the study calcium intakes) or keep the subjects on
their usual calcium intakes; ii) provide of all the food to subjects; iii) perform laboratory analysis to
determine the nutrient composition of the food; and iv) accurately measure the amounts consumed (27).
Regulatory Issues
Currently, there are no Canadian, Australian, or U.K. guidelines regarding the marketing of these “alkaline”
supplements that use the ideas of acid-ash hypothesis and state these ideas as fact.
In 2007, the U.S. Food and Drug Administration denied a proposal for a health claim for potassium citrate
alone or in conjunction with alkaline and earth alkaline citrates, calcium citrate, or high protein diets or
protein supplements for reducing the risk of osteoporosis, as it did not meet scientific agreement
standards (28). Although the statement was published in 2007, there were no changes in the supporting
scientific evidence or the decision as per an update in the year 2015.
Definitions
NAE - Net Acid Excretion: the amount of acid produced from the diet upon metabolism (9).
NEAP - Net Endogenous Acid Production: “the amount of net acid produced by the metabolic
system” (11).
Potential Renal Acid Load: an estimation of the excess of “acid” anions less base (cations) of foods (9).
Key Resources for Professionals
Title: FAQ #2: Alkaline Diet
Description: A document for health professionals, written by a dietitian for the BC Cancer Agency, which
provides background information about alkaline diets and cancer.
Additional Readings for the Professional
Title: Phosphate Decreases Urine Calcium and Increases Calcium Balance: aA Meta-analysis of the
Osteoporosis Acid-ash Diet Hypothesis.
Description: A meta-analysis of studies which quantified the contribution of dietary phosphate intake on
bone calcium excretion in the urine and bone demineralization.
Title: Causal Assessment of Dietary Acid Load and Bone Disease: A Systematic Review & Meta-analysis
Applying Hill's Epidemiologic Criteria for Causality.
Description: A systematic review and meta-analysis of 55 studies on the association of dietary acid load
and osteoporosis development or progression.
Other
Paleolithic Diet
Sometimes the acid-ash hypothesis is used as “evidence” to support the ideas of the Paleolithic diet, and
in this case the Paleolithic diet is said to be plant-based, with little meat and no grains or dairy foods
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PAGE 21
(29).
See Additional Content: Diet Composition - Paleolithic Diet Knowledge Pathway.
References
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Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris RC, Jr. Improved mineral balance and
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Fagherazzi G, Vilier A, Bonnet F, Lajous M, Balkau B, Boutron-Rualt MC, Clavel-Chapelon F.
Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study. Diabetologia. 2014
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Zhang L, Curhan GC, Forman JP. Diet-dependent net acid load and risk of incident hypertension
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Engberink MF, Bakker SJ, Brink EJ, van Baak MA, van Rooij FJ, Hofman A, et al. Dietary acid
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Merck Manual. Metabolic acidosis. 2016. [cited 19 Feb 2017]. Available
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and increases calcium balance: a meta-analysis of the osteoporosis acid-ash diet hypothesis.
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