It’s Complicated: The Relationship Between Milk and Health

  • GutsandGrowth Milestone: this is the 3000th blog post
  • New COVID19/IBD worldwide registry (so far zero cases reported.  Can report cases at the following: SECURE-IBD Registry

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A provocative review (WC Willett, DS Ludwig. NEJM 2020; 182: 644-54) provides a rationale for why a healthy diet may not need milk.

Key points:

  • “The current recommendation to greatly increase consumption of dairy foods to 3 or more servings per day does not appear to be justified.”
  • All the nutrients in milk can be obtained from other sources (including calcium and vitamin D). If diet quality is low, especially for children, dairy foods can improve nutrition. “If diet quality is high, increased intake is unlikely to provide substantial benefits, and harms are possible.”
  • Overall evidence does not support high dairy consumption will reduce fractures
  • Total dairy consumption has not been clearly related to weight control or to risks of diabetes or cardiovascular disease
  • The reported health benefits of milk depend strongly on what food it is being compared to; dairy intake is generally more favorable than processed red meat or sugar-sweetened beverages but less compared to plant-protein sources (eg. nuts)
  • No clear benefit of consuming reduced-fat milk compared to whole milk
  • Milk intake in childhood is associated with greater attained height which confers both risks and benefits

More details:

The authors review the composition of cow’s milk and compare it to human milk and cheddar cheese (Table 1). They note that cows have been bred to produce higher levels of insulin-like growth factor 1 (IGF-1) and that they are pregnant for most of the time they are milked; this greatly increases hormones like progestins and estrogens in milk.

The authors review how milk can promote growth and development in children.  Tall stature, associated with milk intake, is associated with lower risks of cardiovascular disease but with higher risks of many cancers, hip fractures, and pulmonary emboli.

Bone health and fracture risk: “paradoxically, countries with the highest intakes of milk and calcium tend to have the highest rates of hip fractures;” this, however, may not be causal as their are a lot of confounding factors (eg. Vitamin D status, ethnicity).  The authors also note that U.S. studies have shown calcium intake was unrelated to bone mineral density in the hip.  Further, the authors point out the discrepancies between U.S. and U.K with regard to daily calcium requirements; at age 4-8 yrs, U.S RDA is 1000 mg per day compared to 450-550 mg in UK.  Estimation of the calcium requirement is “problematic.”

Body weight and obesity.  “Studies of milk consumption and body weight in children are few and are subject to confounding and reverse causation.”  Available studies, however, have shown that whole milk and 2% milk are associated with lower risk of obesity than low-fat or skim milk.

Blood pressure, lipids, and cardiovascular disease in relation to milk consumption:  Ultimately, whether milk is beneficial is mainly related to the comparison foods.

Milk and the development of diabetes:  intake of dairy products has been associated with a modestly lower risk of type 2 diabetes.  Despite some hypothetical risks for type 1 diabetes, children weaned to “hydrolyzed protein instead of cow’s milk did not have fewer autoantibodies to beta cells after 7 years than children who drank cow’s milk.”

Milk intake and cancer.  Milk consumption is associated with a lower risk of colorectal cancer (likely due to its high calcium intake) and an increased risk of breast cancer, prostate cancer, and endometrial cancer; these effects may be mediated by the sex-hormones in milk.

Allergies to milk may affect up to 4% of infants.  In addition, lactose intolerance “limits consumption of milk worldwide.”

Total mortality and its association with milk intake:  “in a meta-analysis that included 29 cohort studies, intake of milk (total, high-fat, and low-fat) were not associated with overall mortality.”  Again, the risk is related to what food is substituted for milk intake.

Organic/grass-fed production and potential detrimental environmental effects from milk production; the latter includes pollution, antibiotic resistance, and greenhouse gas production.

My take: These authors are not going to get any funding from the dairy industry.  Dairy is typically an important nutrient source in children. Particularly in adults, lower intakes of dairy may be warranted.

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Island Ford, Sandy Springs

The Prosecution Rests…PPIs on Trial

For physicians who use proton pump inhibitors in a cavalier manner, a recent review (CM Stark, CM Nylund. J Pediatr 168: 16-22) provides a sobering reassessment of the potential side effects and potential complications of proton pump inhibitors (PPIs).  After finishing the article, the impression left was of a lawyer putting these medications on trial for high crimes and misdemeanors.

Here were the key points:

Infectious disease: PPI-induced hypochloridia is known to alter the gastrointestinal bacteria motif, allowing certain normally absent or depleted pathogenetic microorganisms to survive and proliferate.  This can lead to all of the following:

  • small bowel bacterial overgrowth
  • increased gastrointestinal infections (including Clostridium difficile, Salmonella, Campylobacter, and acute viral gastroenteritis)
  • pneumonia (particularly community acquired pneumonia and hospital acquired pneumonia)
  • upper respiratory infections
  • spontaneous bacterial peritonitis.

The magnitude of these associations is discussed in detail in the review.

Gastrointestinal disease: Use of PPIs has been associated with an increased incidence of the following:

  •  celiac disease which persisted after excluding prescriptions in the year preceding diagnosis (association does not prove causation)
  • benign gastric fundic polyps
  • rebound acid hypersecretion

Malabsorption: PPIs can affect absorption of multiple nutrients, though more studies are needed, particularly in the pediatric age group.

  • calcium: “there is significant evidence to suggest that PPI use can alter calcium and bone metabolism…associated with an increased risk of hip fractures in older adults….It is reasonable to hypothesize that PPI administration during adolescence and early adulthood could decrease an individual’s peak bone density.”
  • magnesium: PPI have been hypothesized to affect magnesium absorption.  “A study of 366 Canadian patients hospitalized with hypomagnesemia…found PPIs [were] associated with a 43% increased risk of hospitalization.”  More studies are needed to determine the whether this risk is truly significant.
  • iron, vitamin B12, and vitamin C absorption may be affected by PPI use.

Cardiovascular/Renal/Microbiome:

  • Cardiac: In adults, PPI use has been associated with adverse cardiac events.  The pathophysiology could have been pediatric implications.  PPIs can increase asymmetrical dimethylarginine (ADMA) which is an endogenous inhibitor of nitric oxide synthase.
  • Renal: PPIs have been associated with cases of acute interstitial nephritis
  • Microbiome: “PPIs alter the microbiome.”  Decreased diversity of the microbiome has been associated with a large number of medical conditions, including irritable bowel syndrome, inflammatory bowel disease, nonalcoholic fatty liver disease, necrotizing enterocolitis as well as many non-gastrointestinal conditions.  “The temporality of dysbiosis and subsequent disease development has  not been explored fully for most conditions.”

My take: PPIs can be life-saving and disease-altering medications.  At the same time, (per authors) “PPIs should not be prescribed without consideration for all short- and long-term side effects.”

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This Webinar Will Review Issues with Regard to Optimal PPI Usage and Includes My Esteemed Colleagues (Dr. Gold and Dr. Garza)

This NASPGHAN Webinar Will Review Issues with Regard to Optimal PPI Usage and Includes My Esteemed Partners (Dr. Gold and Dr. Garza)

Dietary supplements — safe and effective?

Most people consider dietary supplements as likely to be beneficial but at the very least ‘there not going to make you worse.’  That sentiment is wrong.  A review recently published has shown that some dietary supplements may increase the risk of cancer (Journal of the National Cancer Institute 2012; 104: 732-39).

Nearly half of the US adult population uses one or more dietary supplements but there is very little evidence that these supplements reduce cancer risk; in fact, the contrary is true.  Based on numerous studies, the authors make extensive comments regarding the studies of antioxidants, folic acid, and vitamin D/calcium which are summarized below.

Antioxidants

While observational data has suggested benefits from fruit and vegetable consumption, data on antioxidant supplement consumption has not shown a beneficial effect.  The review highlights a number of studies with regard to β-carotene, vitamin A, vitamin C, and vitamin E/α-tocopherol.  Specifically, vitamin C and E do not protect against total cancer incidence. α-tocopherol and β-carotene do not protect against cancer or cancer mortality.

  • The Selenium and Vitamin E Cancer Prevention Trial (SELECT) followed 35,533 men at average risk for prostate cancer for approximately 5.5 years.  This study was halted due to lack of benefit.  In addition, the extended followup reported that α-tocopherol significantly increased the risk of prostate cancer by 17%.
  • The β-carotene and Retinol Efficacy Trial (CARET) had a 39% increase in lung cancer incidence compared to the placebo arm.
  • In two of three large studies of β-carotene, the intervention increased the risk of all-cause mortality.
  • The Nutritional Prevention of Cancer (NPC) extended followup found that selenium supplementation statistically increased the risk of squamous cell skin cancer by 25% and non-melanoma skin cancer by 17%.

Folic Acid

Folic acid which is a synthetic oxidized form of folate is commonly used in fortification and supplements.  Recent meta-analysis of randomized controlled trials (RCTs) has found no effect of folic acid supplementation on the risk of colorectal adenomas over a 3-year treatment period.  In addition, one study demonstrated an increased risk of advanced colorectal adenomas (relative risk = 1.67).  Also, in observational studies, higher intake of folic acid has been linked with increased prostate cancer risk.

Vitamin D and Calcium

The Institute of Medicine published recommendations with regard to Vitamin D and calcium intake in 2011 and found that “there is not enough evidence to state that there is a causal association between low vitamin D intake and increased cancer risk.”  The authors summarize several conflicting results with regard to breast, colorectal, and prostate cancers. In addition, a recent meta-analysis of RCTs indicated that calcium supplementation was associated with a statistically-increased myocardial infarction risk.

Why are supplements so widespread if they are not beneficial and potentially dangerous?

  • The authors also summarize regulatory efforts.  In 1990, due to unsubstantiated health claims by food manufacturers, Congress passed the Nutrition Labeling Education Act (NLEA).
  • To limit FDA authority over supplements, at the behest of nutritional supplement manufacturers, in 1994 Congress passed the Dietary Supplement Health and Education Act.  This classified supplements as food and limited the role for the FDA.
  • In 2006, in reaction to deaths from ephedra, Congress passed the Dietary Supplement and Non-prescription Drug Consumer Protection Act.  This allows the FDA to collect adverse reports on supplements but did not give additional regulatory powers.

Conclusions from this review

  1. In populations with a high background of normal nutrient status, risk is accentuated if there can be harm at higher doses.  For selenium (in the NPC study), apparent benefits have been confined to individuals with the lowest baseline blood selenium levels.
  2. It is not reasonable to assume that consumption of a single nutrient would exert a chemopreventive effect equally in all tissues.  In addition, there are substantial variations in formulations and doses of supplements available.
  3. Efficacy and harm are typically tested over several years.  Given the natural history of cancer, it may take decades to assess supplement impact.
  4. Multiple consensus recommendations have indicated that supplements do not prevent cancer and do not prevent chronic disease (Table 1 in reference).  The most recent was from the American Cancer Society in 2012. “Present knowledge indicates that dietary supplements do not lower cancer risk.”
  5. Despite the evidence, the authors note that believers in supplements are unlikely to accept ‘mainstream’ science.  Some may think that unconventional treatments are ignored by science for monetary reasons. Some may think that these products are regulated and would not be offered if they were not beneficial.

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