Absolute vs. Relative Risk

This is going to be a dull and numbers-heavy statistics post, there’s no way around it. But the concepts of absolute and relative risk are fascinating and eye opening once you learn how they can mislead. Absolute risk simply refers to the risk of a disease or condition happening to someone with a certain characteristic over time, expressed as a percentage. For example, the absolute risk of a smoker getting lung cancer is 10-15%. Relative risk compares the risks between two or more groups of people relative to each other, such as vegans and non-vegans, or people given a drug and those given a placebo. For example, processed meat eaters are 18% more likely to develop colon cancer than people who shun processed meat. Why do these matter when we’re thinking about whether or not to take a drug or engage in some healthy or unhealthy behavior? 

This article explains it well. Often research studies highlight relative risk reduction to make the benefit of a drug MUCH larger than it actually is. A study might report that a drug halves the risk of a certain event happening, but in reality the risk of that event happening is already so small that the risk might go from 2% to 1%, hardly a noticeable decrease but technically the risk has been decreased by half (50%). Often the public doesn’t have access to full research articles and can only see abstracts or sensational headlines reporting the larger numbers. 

Take statins. They’re one of the many drugs whose benefit is often overstated (and here I’m going to round the numbers a bit to make the math easier). Frequently, studies will report somewhere around a 25% drop in coronary-related deaths for people taking a statin compared to those not on a statin, but what does the data say? In placebo groups, the risk of coronary-related death is around 8%, and in treatment groups the risk is around 6%. The researchers get the 25% by saying that 6 is 25% smaller than 8. It is. But here are the hard numbers: if we have 100 people in each group, 8 would suffer coronary deaths in the placebo group and 6 people would suffer coronary deaths in the statin group. By giving 100 people a statin, 2 extra people will not experience coronary-related death. It’s beneficial of course, but we can’t forget drugs have side effects.

Here’s another example with a diagram (I’m only using this diagram because I think it depicts the concepts clearly - let me be clear that processed meat is troublesome for many reasons and not just bowel cancer!!). If we have 100 people not eating processed meat, 5.6 of them will get bowel cancer. If we have 100 people eating processed meat, 6.6 of them will get bowel cancer. Thus 1 extra person out of every 100 people will get bowel cancer if they eat processed meat. What about the 18% figure that we discussed in the beginning of this blog? It comes from the fact that 6.6 is 18% higher than 5.6.

Source: euphic.org

  Another concept along these same lines is NNT, or Number Needed to Treat. It refers to how many patients need to be treated to see one patient receive a benefit. For example, 1,667 people need to take the drug Aspirin on a daily basis for a year for one heart attack to be prevented. For sinusitis, 17 people need to be given antibiotics for one to see a benefit.  

 Bottom line: The above has been an abbreviated explanation of these concepts, so if you’d like to read further please see some resources below. If we’re talking about a drug, ask your doctor about how many people need to be treated with the drug they are prescribing for one person to see a benefit, and always ask them about the potential side effects.  

Other Resources: 

The NNT

Article by Stanford professor re: statins 

Rebuttal to statin study

As explained by an MD

Drug-Induced Nutrient Depletions

One of the hidden costs associated with medications is that many of them can lead to depletions of certain micronutrients (vitamins and minerals) in our bodies. I was entirely unaware of this until I studied nutrition -- no doctor had ever even mentioned this possibility for any of the medications I had been prescribed at one point or another. Here’s one chart that shows the extent of depletions across just a few commonly prescribed drugs including antibiotics, acid blockers, statins, oral contraceptives, and antihypertensives. Additionally, this is one of my favorite sites that allows you to type in the name of a medication and it returns a list of possible nutrient interactions with the scientific reference from PubMed. It’s by no means a comprehensive database, but it can help highlight nutrients of concern. One major caveat is that studies are often conflicted about which nutrients are depleted, if that depletion actually leads to clinically significant symptoms, and if supplementation is warranted. I think that’s why there’s rarely consensus among providers around replacing certain nutrients.   

Anti-acid medications, especially the proton pump inhibitors (PPIs), are suspected of putting people at risk of several deficiencies due to their mechanism of action of blocking the production of acid that facilitates the absorption of iron (especially iron from non-animal sources), B12, magnesium, and zinc. This article from the Mayo Clinic reports a likely causative association of PPI use with low magnesium and low B12 levels.

I’m especially mindful of vegans and older adults who are on these medications long-term as these populations are already at risk of not getting enough B12. Furthermore, according to the FDA (the FDA! Not this overly-cautious dietitian), PPIs are NOT supposed to be taken for more than a 14-day course, yet people are often on these for years.  

Statins, cholesterol-lowering drugs, are commonly prescribed (25% of the adult population is on one) and have been found to deplete an antioxidant called CoQ10. Our bodies can produce this antioxidant, though we do get it from diet as well. It is a critical piece of the electron transport chain and thus essential for energy production. One of the major side effects from statins is muscle pain / weakness with a likely culprit being the depletion of CoQ10. A recent review article mentions that “tissue deficiency can occur due to medications such as statins” and this meta-analysis of 12 randomized controlled trials reported that supplementation [of CoQ10] did indeed ameliorate muscle-related symptoms (pain, weakness, cramping). The majority of the studies focus on muscle pain, but deficiencies of CoQ10 can also lead to fatigue and exercise intolerance. 

Like everything in health and nutrition, studies are often mixed and some have found that supplementation doesn’t help muscle pain and thus many providers advise against taking CoQ10. But knowing that statins DO deplete blood levels of nutrients (CoQ10 isn’t the only one), shouldn’t we be concerned about that fact alone? Who knows what other consequences are happening that studies haven’t yet measured? 

 If I were on a statin I would most definitely supplement with CoQ10, somewhere in the realm of 50-200 mg (some people may need higher levels if they’re symptomatic). As far as I know, studies have either suggested a benefit or at worst no effect from supplementation, so given this I’m not quite sure why more doctors don’t recommend taking a supplement given that the side effects from the supplement are rare and minor if they occur. The level of CoQ10 can also be measured in the blood, and although it’s not a perfect measurement (most of it is in the cell and not in the bloodstream), it is at least a piece of data that you can ask your doctor to check.  

Another medication, metformin (for glucose control), has been found to be associated with B12 deficiency (here and here). And oral contraceptives can deplete a slew of nutrients.  

I’ll stop here, but my motto in all of this is: why risk it? If there’s even a slim chance that certain drugs can cause specific nutrients to be depleted or not absorbed as well as they should be, why not focus on certain foods containing the nutrients in question or (as in the case of B12) take a reasonable supplemental dose?

Iron

The term “anemia” often gets tossed around by omnivores who are concerned that their newly-vegan friends will become anemic without slabs of red meat. Furthermore, most people automatically assume anemia is related to iron deficiency, but anemia can in fact be caused by deficiencies of other nutrients, such as vitamin B12, folate, vitamin E, and copper. Here I’ll just discuss some things to consider about iron. Iron is involved in energy production, thyroid hormone production, transport of oxygen, immune function, and DNA synthesis. Numerous chronic diseases and conditions put individuals at risk of iron deficiency such as Celiac disease, bariatric surgery / gastrectomy, hypothyroidism, COPD, chronic kidney disease, Crohn’s, H. pylori infections, ulcerative colitis, and heart failure. Medications (proton pump inhibitors, anticonvulsants, metformin, chemotherapy) can also decrease iron absorption or utilization. 

The recommended daily allowance (RDA) for iron for vegans is 1.8X the amount recommended for omnivores because vegans must get iron exclusively in the form of non-heme iron (animal products contain heme iron which is absorbed a bit easier). Technically this means vegan women should get 32 mg/d, a high bar for women to obtain and one I think is too high. The tolerable upper intake level is 45 mg/d for adult men and women which isn’t much higher than the 32 mg/d recommendation. Some people (myself included) are genetically predisposed to have higher than normal levels of iron which will likely show up on a blood test, so care must be taken not to overload.   

Measuring iron stores: 

Investigating anemias and iron status isn’t always as simple as just looking at hemoglobin/hematocrit, as those are the last markers to change when iron stores are low. One of the best markers of iron status is ferritin (an iron storage protein), but note the wide reference range labs may use. Always obtain a copy of your labs from your doctor to check your values to make sure you’re not at the very bottom or top of the reference range. Ferritin can skyrocket in the presence of inflammation so it’s not always reliable. Your doctor might run an iron panel measuring things like the amount of free iron circulating in your blood and the affinity of your cells for iron.  

Getting enough iron: 

If your doctor recommends getting iron through food and not supplementing, great vegan food sources of iron are: bran flakes, cream of wheat, dried prunes, spinach, tofu, extra dark chocolate (yes!), soybeans, and dried beans or lentils. Check out this post for other food sources of iron. If you’ve gone through a thorough workup and your doctor has uncovered an iron-deficiency anemia, they may prescribe a specific dose of iron to correct the deficiency. Certain forms of iron can be quite constipating and harsh on the digestive tract though, so if you can’t tolerate one form do try another such as ferrous bisglycinate or look for a label that indicates “gentle,” “well-tolerated” or controlled-release forms.  

Bottom line: Iron status can be a tricky beast in the setting of veganism, chronic disease, medication usage, and genetic predisposition. If you don’t need to restrict iron, focus on the iron-containing foods above and get labs checked yearly. Your doctor should let you know if you either need to restrict iron or if you need to supplement it.      

Sources and Further information: 

Vegetarian Resource Group

PCRM Nutrition Guide  

Solgar Gentle Iron 

ConsumerLab

How to Make Whole Plant-based Foods More Digestible

When people transition to a whole-foods plant-based diet, they often experience digestive issues because the fiber content of naturally vegan foods can be significantly greater than animal-based foods. Animal foods contain no fiber, not even a single gram. I’ll discuss the benefits of fiber in another post, but for now know that adults need at least 25-38 grams per day. New vegans often become discouraged when they swap an animal product with zero grams of fiber for something like a bean dish that can have upwards of 10 grams per serving, and then feel uncomfortable. The beans are much healthier but it can take some time to get used to them, so go slow. Here are 6 tips for increasing your ability to digest fruits, vegetables, grains, legumes, nuts, and seeds.  

• Start with lower fiber plant foods and work your way up to higher fiber plant foods. Fiber content varies greatly even among similar fruits and vegetables. For example, a cup of raspberries has 8 grams of fiber, whereas a cup of strawberries has 3 grams. See this chart for a sample of the fiber content of foods.  

• Choose more cooked foods. Heating foods helps break down the cell wall. It’s much easier to eat stir-fried broccoli florets compared to a dense stalk of raw broccoli.    

• Beans are some of the most nutritious foods but they contain a complex sugar that we don’t have an enzyme to digest (alpha-galactosidase). 

  • Start with ¼ cup at first and slowly work your way up. 

  • Choose smaller beans like lentils, mung beans, or adzuki beans. 

  • Soak dried beans (though not lentils) overnight for 12-24 hours, rinse, and discard the soaking water prior to cooking. Add a strip of seaweed (kombu) or a bay leaf to the cooking water as these can help break down the indigestible sugars. 

  • Certain brands of canned beans like Eden Foods already add seaweed to help with digestibility. 

• Sprouting and fermenting: these techniques break down certain components such as phytic acid that typically make foods harder to digest. I haven’t tried to sprout anything in my kitchen because I can’t even keep air plants alive, but if you’d like to try sprouting at home here’s a guide. Otherwise you can look into buying products like Truroots (sprouted lentil blend, organic quinoa), sprouted grain English muffins, and sprouted pumpkin seeds. 

• Blend foods: there is no shame in blending up smoothies or soups! No fiber is lost, it’s just broken down so your system doesn’t have to do as much work. Here’s an example of how to build a smoothie from No Meat Athlete (though I wouldn’t put in as much fruit, maybe choose 1). 

• Chew! Please chew. This isn’t just for physically breaking down your foods. Chewing also triggers the release of digestive enzymes in the mouth (for carbohydrates and fat) and signals the release of other hormones in the GI tract that influence digestion.     

Bottom line: The above are a few tips to start making fibrous foods easier to digest and absorb -- so don’t give up just yet if you can’t handle large leafy green salads or vats of bean chili!

Iodine

Iodine is one of the trace elements that plays a key role in thyroid function and metabolism. It’s a special concern for vegans, but it’s also one of the most common nutrient deficiencies worldwide. Somewhere between 1.5-2 billion people around the world likely have suboptimal intake, mainly due to variable soil content and lack of salt fortification. Adults need 150 mcg daily, and pregnant women need 220 mcg daily because deficiencies can lead to growth retardation and neurodevelopmental issues in the baby. In adults, deficiencies can manifest as goiter (an enlarged thyroid gland) and hypothyroidism because iodine molecules are essential parts of thyroid hormones. Interestingly, too much iodine can also increase the risk of hypothyroidism and autoimmune thyroiditis (Hashimoto’s). 

Where do vegans get iodine from? The few notable vegan sources of iodine are sea vegetables (such as kombu, wakame and dulse) and iodized salt. Omnivores get it from seafood, and it’s also found in significant amounts in milk partially because iodine solutions are used as “teat dips” to clean cow’s udders. Personally I don’t want to be getting my trace elements from remnants of a cleaning solution. Unfortunately plant milks are not reliable sources of iodine and many people struggle to eat sea vegetables. If you’re not salt-sensitive and don’t have blood pressure issues, it’s worth using iodized salt: ¼ tsp provides 75 mcg iodine, half the daily recommendation for non-pregnant adults. 

Processed foods, while they may be extremely high in sodium, usually don’t contain iodized salt and are not a reliable source. Sea vegetable supplements and supplements that feature “iodine from kelp” are also unreliable: ConsumerLab reports that half of the kelp supplements they tested contained twice the amount of iodine listed! 

How do I test my iodine status? It’s tricky. Medscape reports that “no test can reliably diagnose iodine deficiency in individual patients.” Population-level iodine status is measured via urinary iodine, but it’s been found to be inaccurate on individual levels because values fluctuate so much with daily intake. One option is a 24-hour urine collection, but that’s cumbersome and again depends on recent intake. Because deficiencies will show up mainly as thyroid issues in adults, it’s very important to have complete thyroid labs measured yearly.  

Bottom line: For my vegans, if you’re not salt-sensitive, use iodized salt and not kosher or Himalayan sea salt. If you like sea veggies, go for it, but avoid kelp. Otherwise I recommend getting iodine as part of a multivitamin/mineral as either potassium iodide or sodium iodide (aim for 100-200 mcg daily).  

Source and Additional Reading: American Thyroid Association 
Gropper, S. A. S., Smith, J. L., & Groff, J. L. (2009). Advanced nutrition and human metabolism. Australia: Wadsworth/Cengage Learning.

Direct-to-Consumer Nutrition Genetic Testing: Is it worth it?

A couple of years ago, I submitted my raw 23andMe data to several companies for nutrition and wellness analysis. These companies put out reports that suggest predispositions based on combinations of gene variants. Instead of yielding clear and helpful guidance, it made things much more complicated. The results were often contradictory, unclear, useless, or verifiable by other means. 

Sensitivity to Dietary Fat 

One company noted that I have a “higher sensitivity to fat” and recommended I get precisely 15% of my calories from polyunsaturated fatty acids and 12% from monounsaturated fatty acids. Food labels don’t separate fat into monounsaturated vs. polyunsaturated fat, and nearly all fats have varying proportions of both, so I’m not sure how they expect consumers to reach this level of precision. 

Another company came up with an entirely different conclusion: “You are less sensitive to saturated fats...you can consume more saturated fats-rich foods than average without a high risk of obesity.” This was excellent news to my chocoholic ears. Yet a third company reported “a highly-sensitive cholesterol response to eating dietary fat” and suggested I consume 15% of daily calories from fat. That’s a very different recommendation than the first one suggesting 15% of fat just from polyunsaturated fat!  

Carbohydrate Sensitivity 

Two out of three companies suggested a “high sensitivity” to carbohydrates and to aim for a daily glycemic load of 70. Who calculates daily glycemic load?? It’s impractical and nearly impossible to tabulate and track. Furthermore, our response to carbohydrates very much depends on the type of carbohydrate (are we talking about jelly beans or kale) as well as the type and quantity of fat and protein consumed.   

 Vitamin Requirements 

According to one company, I have a “raised” vitamin D requirement, to at least 800 IU daily. A second company says I’m “less likely to have lower blood levels of vitamin D due to increased ability to transport vitamin D in the body.” My own personal experiment suggests the former, but this sort of data is probably best monitored by a routine blood test and not a genetic prediction. Furthermore, many of these companies also sell their own supplements after making personalized supplement recommendations to consumers!! 

Extraneous Information 

23andMe suggests I’m likely to wake up at 8:23 AM. Interesting, but completely useless and inaccurate. I have not slept past 8 for approximately 10 years. Many companies also report on caffeine sensitivity, but I’ve yet to meet a client or friend who is unaware as to the effects of caffeine on their bodies. They all know without a test whether they become jittery after a sip of Starbucks or whether they can enjoy an after-dinner cappuccino.

Bottom line: Don’t waste your money just yet. Perhaps these companies have improved their predictive abilities since I submitted my raw data to them a while back but I don’t think these reports should be used by dietitians or other health care providers for all the reasons listed above. Much of the “individualized” advice provided was extremely basic nutrition information that could be applied to the general population. Trust your own symptoms and reactions to food, make sure you get lab tests yearly to check things like vitamin D and B12, and aim for a balance of carbs, fat, and protein from whole plant foods on a daily basis.   

Additional Reading and Sources

https://www.todaysdietitian.com/newarchives/0519p36.shtml

B12

Most people new to a plant-based diet will have already heard concerns about getting enough B12. The recommended daily allowance for adults is 2.4 mcg daily, but it’s essential that ALL vegans supplement. 

What does B12 do? B12 is involved in helping create DNA and red blood cells, producing energy, and contributing to immune and nervous system functioning.

Are vegans the only ones at risk of deficiency? No! According to the NIH, up to 15% of the population may be deficient. Among those most at risk include older adults with low stomach acid, individuals on acid-suppressing medications, people with GI disorders such as Celiac or Crohn’s, or those who have had bowel surgeries.  

Countless medications have been found to lower the amount of B12 available to the body in some way, including: valproic acid, decadron, diuril, dexamethasone, colchicine, erythromycin, metformin, hydrocortisone, prednisone, proton-pump inhibitors (Prilosec, Prevacid, pantoprazole, Nexium), H2 blockers (Pepcid, Zantac), anticonvulsants, birth control pills, and aminosalicylic acid.

What signs and symptoms may result from a deficiency? There are many nonspecific signs and symptoms including anemia, depression, fatigue, memory loss, neuropathy, and tingling in the extremities. 

Should I ask my doctor to test for it? Serum B12 is not really a great marker of B12 status because “concentrations can be maintained at the expense of tissues, a person may exhibit normal serum concentrations but have low tissue concentrations” (Advanced Nutrition and Human Metabolism). A better marker is methylmalonic acid (MMA), which, if elevated, suggests a B12 deficiency, because B12 is needed to convert it into another substance. If there’s not enough B12, methylmalonic acid will build up. MMA can be measured either in blood or urine. Homocystine is another substance that will also be elevated if B12 is insufficient, but it’s not specific for B12 and can be elevated for other reasons. An elevated mean cell volume (MCV) may also be found, indicating that the volume of your blood cells is larger than it should be; though again, it’s not specific for B12. 

Did you know? Meat eaters will often use the necessity of B12 supplementation as an argument against veganism, but most don’t realize that the animals they eat are being heavily supplemented, and not just with B12! Swineweb says “Because of the variability of vitamins in natural swine feedstuffs and the relatively low cost of commercial vitamins, it is recommended that producers provide the following vitamins completely from the vitamin premix and disregard amounts in the feed. These are vitamin A, D, E, K, riboflavin, niacin, pantothenic acid, choline and B12.” And on minerals: “Usually, a commercial mineral supplement will meet the needs of most classes of cattle.”

Bottom line: Take a B12 supplement daily, at least 50 mcg. It’s cheap. Symptoms of deficiency are vague. Testing can be inconclusive.  

Sources and Additional Reading: Consumer Lab; University of Missouri Extension; Academy of Nutrition and Dietetics

Gropper, S.S. and Smith, J.L. (2018). Advanced Nutrition and Human Metabolism. Boston, MA: Cengage.