• lipid lowering
• biomarker
• nutritional treatment

Lipoprotein(a) (Lp(a)) is an important and causal risk factor for cardiovascular disease (CVD).1 There are 1.43 billion people (approximately 20%–30% of the population, with some racial variations) with an elevated Lp(a) >50 mg/dL and 2%–3% with a very high Lp(a) >100 mg/dL, which translate into moderate (+80%) or strong (+300%) increase in CVD risk, respectively.2 Due to its genetic basis, once in a lifetime measurement of Lp(a) is currently considered sufficient for risk assessment.

I am a physician specialised in preventive medicine with no family history of CVD. I discovered my own Lp(a) at 97 mg/dL in 2004 (with a maximum Lp(a) of 108 mg/dL measured in 2013). As there were no effective treatments to lower Lp(a) in 2004, I decided to start rosuvastatin 10 mg/dL, which I have taken since 2005. Low-density lipoprotein (LDL) cholesterol fell to 80–90 mg/dL on average.

From 2004 to early 2018 I consumed a Mediterranean-style diet with 200–250 g of carbohydrates (CH) per day, while exercising 7–10 hours per week. As a hobby triathlete, I learnt about the effects of a very-low-carb ketogenic diet (VLCKD) on long-term endurance.3 In spring 2018 I went on VLCKD (50–80 g of CH=<10% enCH). In the same season I remeasured my Lp(a), which fell to 65–70 mg/dL on separate occasions (table 1).

The lab’s assay (DiaSys Lp(a) 21 FS a) remained unchanged since 2004. This Lp(a) assay has high accuracy, with an intra-assay and interassay SD of 0.528–1.08 mg/dL, as reported by the manufacturer. MVZ Labor Dr Riegel is a certified German laboratory in accordance with DIN EN ISO 15189.

The observed large variation in a ‘genetically determined’ risk factor motivated me to do a n=1 nutrition experiment. In July 2020 I switched from VLCKD to a high-carb-low-fat (HCLF) diet with an average intake of >400 g of CH per day for 2 weeks. Nutrition protocols were documented in the nutrition app ‘Ernährung Pro’. Weight was unchanged at 89 kg (body mass index 24.9 kg/m²). Statin therapy was unchanged with 10 mg of rosuvastatin at night. Physical activity levels were kept constant at 2 hours per day on average.

As shown in table 1, Lp(a) was measured at 67 and 69 mg/dL before the change and went up to 95 and 101 mg/dL after 14 days on HCLF diet. When I went back to VLCKD, Lp(a) fell again to 80 mg/dL after 2 weeks and to 74 mg/dL after 3 weeks. While on VLCKD, mild ketosis (beta hydroxybutyrate level 0.8 mmol/L) was documented with FreeStyle Libre.

To my knowledge this is the first observation of such a large change in Lp(a) induced by dietary modification. I was unable to find any diet study done in patients with a very high Lp(a). A recent review examined the effect of dietary interventions on Lp(a),4 but baseline Lp(a) was normal in all seven studies. The changes in Lp(a) of 10%–20% or 2–5 mg/dL, which were reported in this review in participants with normal baseline levels of Lp(a), have no clinical relevance.

On the other hand, if a very high Lp(a) of >100 mg/dL could be lowered by a dietary intervention to below 70 mg/dL as documented here, this might well translate into a significant risk reduction for CVD.

Possible mechanisms for an increase in Lp(a) on a high-carb diet include insulin mediation, as my HOMA index increased substantially while consuming high-carb diet. Insulin is a potent regulator of de-novo lipogenesis in the liver via transcription factors CHREB-P and SREB-P. It is well known that an HCLF diet compared with a Low-Carb-High-Fat (LCHF) diet will increase apo-CIII, triglycerides, very-low-densitiy lipoprotein (VLDL), apolipoprotein B and small-dense LDL particles.5 To exclude possible confounders, physical activity levels were kept constant during the experiment, as was the average wine consumption with dinner. There were no infections present (normal high-sensitive C-reactive protein (hs-CRP)) when blood samples were taken, so it is very likely that the change in CH ingestion from <50 g/day to >400 g/day is causally related to the changes in Lp(a).