Can a 3-day fast reset your immune system?

Background

That is the title of a Forbes article by contributor Steven Salzberg. It summarizes a study on autophagy (the body's mechanism of degradation and recycling of cellular components), with focus on the immune system:

USC's Valter Longo, who studies aging and longevity [...] described remarkable metabolic changes that occurred as a result of prolonged fasting. They found that fasting for 3 days or longer -- drinking only water and eating less than 200 calories per day -- can truly "reset" some components of your immune system.

They found that fasting lowered white blood cell (leukocytes) counts, which in turn triggered the immune system to start producing new leukocytes, a key component of your body's immune system.

The research looked at both mice and humans. The results indicate that a 3-day fast (but not a 1-day fast) was beneficial for cancer patients pre-chemotherapy.

That is promising. Let's see what it can do for a healthy individual such as myself (mid-30's, caucasian male). Would it reduce the inflammation in my nasal mucosa? (I wake up with one nostril congested every morning.) Will it improve my skin condition?

I was also aware of caloric restriction as an anti-aging mechanism in general, so fasting was an idea I'm comfortable with.

Fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.

Incidentally, on March 24 at 2pm I was scheduled for a blood draw for an InsideTracker test, so I decided to continue the fast.

How to fast without starving

I wasn't eating that much to begin with; probably under 1500 calories per day. Nevertheless, dropping down to 200 calories should be scary, right? Well, not really. Guess how many calories are in the meal below.

Tuna and carrots

That is 140 grams of diced carrots (super convenient to prepare in the microwave if you're short on time; they come in a self-venting bag) and a can of Chunk White Albacore Tuna (in water, no salt added, 5oz). A grand total of 60 + 100 calories (I didn't count the lime slices). I've just had this meal and it's pretty filling. Note that this is a double serving of both carrots and fish, so you could get by with just 80 calories per meal and split them across the day.

For dinner, I had a serving of ceviche - no preparation, delicious taste, and only 45 calories.

Other nice snacks that taste good:

But the most general way to find filling and nutritious foods is at NutritionData.Self.com:

InsideTracker web page

The bottom line:

  1. split your meals across the day
  2. eat filling foods
  3. drink lots of water

Results

TL;DR - lost 3 lbs, marked increase in strength (pushups count went from 25 to 35), no change in nasal congestion or skin condition, slight cognitive enhancement.

Day 1 - Tuesday March 24, 2015

Day 1 was the easiest - didn't feel that hungry, and not much changed.

I ate 205 calories - a stuffed pesto mushroom, and a serving of ceviche.

2pm: blood draw at LabCorp. Fasting since midnight.

Body composition at the end of the day: 156.9lbs, 22.9% body fat, 38.1% lean muscle.

Day 2

Day 2 was more difficult - I felt more hungry, and noticed some minor decrease in attention. I can't attribute this to the fasting though - I had noticed worse attention on other days, and the culprit was most likely too little sleep, which happened on day 2 as well.

I ate 185 calories - two servings of ceviche (90 calories), about 60 calories worth of raspberries, and a cheese wedge (35 calories).

Day 3

Indeed, it took more than 48 hours to see positive results.

At 60 hours in, my military pushups count jumped from 25 the previous day, to 30. It felt significantly easier to do the pushups, and I could have done more, but I wanted to keep good form.

I ate 200 calories: 160 for lunch (the carrots and tuna pictured above), then a little less than a serving of ceviche for dinner, and 10 raspberries before bed.

Final day - March 27, 2015

Another jump in the military pushups count to failure: 35! This is close to my personal record of 37, which I had attained after sustained training. No such training this time.

12:30pm: blood draw at QuestDiagnostics

Body composition after the blood draw (12 vials) and one CLIF Bar (which should cancel each other out): 154.0lbs, 22.1% body fat, 38.6% lean muscle.

This indicates a loss of 3lbs of body mass. The body composition was determined using an Omron HBF-516B full-sensing bioelectrical impedance analysis scale, so the changes in fat and lean muscle percentage can't be considered significant.

Biomarkers

Thanks to InsideTracker CSO Gil Blander, who sponsored the tests, we have "before" and "after" biomarkers. InsideTracker happened to change labs (LabCorp to QuestDiagnostics) exactly in the middle of my test, but I was reassured that the measurements are very similar, since LabCorp and QuestDiagnostics are the best labs in the US. However, the machine error between tests, even with the same provider, is 10%. As such, changes of 10% or lower should not be regarded as significant.

Biomarker changes

Excluded biomarkers

Since LDL and UIBC weren't measured by Quest, I didn't include them in the comparison. Also, the biomarkers in the Liver Enzymes Group (ALT, AST, GGT, Albumin) changed very little (by about 1%). They were also all in the optimized zone, so I didn't include them in the charts.

Expected biomarker differences

The main effect of this intervention that I was hoping for, was a reduction in inflammation. Two biomarkers for inflammation are white cell counts and CRP. How did these change?

  • White blood cell count decreased from 5.2 to 4.7x10E3/uL and remained in the optimized zone.
  • The high sensitivity test for C-Reactive Protein (hsCRP), a marker of inflammation throughout the body, showed a jump from 0.5 to 0.9 mg/L, out of the optimized zone, and barely below the average risk of developing cardiovascular disease (<1.0 mg/L; 0.5 mg/L is clearly in the "low risk" zone).

Based on these two biomarkers, it doesn't seem that the fast provided much benefit. My nasal congestion and skin condition showed no change. Gil didn't have any particular insight into this. It's possible that the white blood cell count dropped, then new leukocytes were produced as the cancer patients study suggests, but we can't distinguish between the two types of cells.

Notable biomarker differences

Other biomarkers showed more significant changes:

  • Fasting glucose dropped from 92 to 70 mg/dL. Gil said that was a desirable change and something he expected. Lower values that are above 64 mg/dL are good for healthy adult males.

  • Triglycerides almost tripled from 36 to 105 mg/dL, within the normal range but above the optimal zone (100 mg/dL or lower) recommended by the American Heart Association. Gil's comment: the spike was due to fat being broken down during the fast by the liver. This is good for those who target fat loss, but it should be mentioned that fasting will break down muscle as well.

  • Cortisol doubled, from 9 to 17.5 ug/dL. Note that there was a measurement problem, in that cortisol levels should be measured in the morning, while my tests were done at 2pm and 12:30pm. Only Quest brought up this aspect, so I'm not sure if InsideTracker compensated for both or only the second test. Gil mentioned that the spike in cortisol is expected due to the stress imposed by the fast.

  • Folate (Vitamin B9) almost doubled, from 12.2 to 20.8 ng/mL, into the "high" zone. From InsideTracker:

    High levels of folic acid may mask Vitamin B12 deficiency and may affect the health of the nervous system.

  • Free testosterone dropped by 20%, from 10.4 pg/mL to 8.2 pg/mL, below the optimized range. InsideTracker advises that "Athletic performance suffers when free testosterone is low, because of decreases in lean muscle mass, energy, and competitive drive". I haven't tested my athletic performance in raw terms, but the push-ups performance increased from 25 before the fast to 35 after.

  • Sex Hormone Binding Globulin (SHBG) increased by ~50%, and got into the "very high" range (64 nmol/L). You don't want this to happen, because

    SHBG inhibits the function of testosterone. Thus, bioavailability of testosterone is influenced by the level of SHBG. If you have too much SHBG, it binds more sex hormones and prevents these hormones from being active. If you don't have enough active sex hormones, your sex drive, your overall energy level, and your memory all suffer.

    On the last night of the trial, my sexual performance was significantly lower than my average, yet nothing that led my partner to complain.

  • Ferritin increased by 30%, jumping even higher in the "High" range, to 306ng/mL. InsideTracker advises that "fatigue is sometimes a symptom of elevated ferritin"; however, I felt a lot more energized during the fast, to the point of having acute insomnia for two nights. However, 306ng/mL is outside of the normal range according to most laboratories. Wikipedia mentions an interesting study on ferritin excess:

According to a study of anorexia nervosa female patients, ferritin can be elevated during periods of acute malnourishment, perhaps due to iron going into storage as intravascular volume and thus the number of red blood cells falls.1

  • Iron dropped by 30%, into the optimized zone (121 -> 83 ug/dL). According to InsideTracker, "your body does not have any biochemical ways of removing iron. Instead, iron is lost through processes such as bleeding, menstruation, and breast-feeding." None of that happened during this trial, so I wonder if this is a measurement error, or misleading figure caused by the artificially low ferritin level explained above.

  • Transferrin saturation dropped into the optimized zone: 42% -> 31%.

  • Vitamin D dropped by 20%, from 44 to 36 ng/mL.

  • Sodium dropped into the "low" range, from 140 to 134 mmol/L. The percentage drop is small, but the optimized zone for sodium is narrow as well: 137 to 146. In fact, a value of 134 mmol/L qualifies as hypoanatremia. This was likely caused by inadequate supply of sodium in the little food I ate, combined with increased sodium excretion during starvation - a common problem with fasting.2 I might also have been extra water to quench hunger. Bottom line: supplement with sodium when fasting.

  • Zinc dropped by 15% (115 -> 97ug/dL), back into the optimized zone. See my article on zinc.

Conclusion

Is fasting for three days worth it? While my situation was relatively gray, based on the particular biomarkers you want to improve, it might be a good idea. You might also find that you feel better subjectively (stronger and more alert).

Please do leave a comment if you have a different understanding and interpretation of the biomarkers, or insight into how close LabCorp and QuestDiagnostics typically are. I hope that this data will help others who want to optimize specific areas of their health.

Footnotes


  1. Kennedy A, Kohn M, Lammi A, Clarke S (2004). "Iron status and haematological changes in adolescent female inpatients with anorexia nervosa". J Paediatr Child Health 40 (8): 430–2. []PMID 15265182](https://www.ncbi.nlm.nih.gov/pubmed/15265182). ↩

  2. "During starvation there is increased sodium excretion and a negative sodium balance even when a sodium supplement is given." - David M. Gozansky and Robert H. Herman. The American Journal of Clinical Nutrition 24: July 1971, pp. 869-871. ↩

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